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Medicinal chemistry in popular culture: an analysis of the representation of bioactive substances in cartoons and games

Aldo S. de OliveiraI; Angelica JustinoII; Thiago H. DoringI; Vanessa NascimentoIII,*

I. Departamento de Ciências Exatas e Educação, Universidade Federal de Santa Catarina, Campus Blumenau, 89036-004 Blumenau - SC, Brasil
II. Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Campus Florianópolis, 88040-900 Florianópolis - SC, Brasil
III. Laboratório SupraSelen, Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-141 Niterói - RJ, Brasil

Received: 08/20/2024
Accepted: 10/30/2024
Published online: 12/20/2024

Endereço para correspondência

*e-mail: nascimentovanessa@id.uff.br; aldo.sena@ufsc.br

RESUMO

This study investigates the representation of bioactive substances in popular culture, with a special focus on cartoons and games, through the lens of Medicinal Chemistry. We explore how these substances, often complex in their composition and effects, are reinterpreted and simplified to fit into fictional narratives, influencing the public perception of science. Taking iconic examples such as "Alice in Wonderland", "Mario Bros", "Popeye", and "Asterix and Obelix", we analyze not only how science is interpreted but also how it is transformed into narrative elements, fueling imagination and shaping cultural perceptions. Furthermore, this research aims to fill a gap in the literature by introducing a multidisciplinary approach that integrates concepts of Medicinal Chemistry with media analysis and molecular modeling. The inclusion of these novel data and analyses not only enriches our understanding of representations of psychoactive substances in popular culture but also provides valuable insights for research in Medicinal Chemistry and the development of future pharmacological therapies. By highlighting the importance of public science communication and media literacy, this study contributes to promoting critical thinking and a broader appreciation of the intersection between science, popular culture, and entertainment.

Palavras-chave: media representation; bioactive substances, games, cartoons.

INTRODUCTION

Medicinal Chemistry, situated at the confluence of chemistry, physics, biology, and medicine, constantly seeks innovations to advance disease treatment and our understanding of biological mechanisms.1 However, the complexity of pharmacological concepts and structure-activity relationships can pose a significant obstacle in teaching these fundamental disciplines.2 We propose an innovative pedagogical approach that utilizes popular culture - including movies, games, and comic books - as a teaching tool to elucidate and contextualize concepts of Medicinal Chemistry. Through the analysis of narratives such as "Alice in Wonderland", "Mario Bros", "Popeye", and "Asterix and Obelix", this work investigates how fictional pharmacological elements can serve as a basis for education in Medicinal Chemistry, transforming learning into a more engaging and accessible experience.

Natural products have long been a cornerstone in the field of Medicinal Chemistry, serving as a critical source of bioactive compounds with therapeutic potential. These naturally occurring substances provide unique molecular frameworks that are often complex and diverse, offering advantages in drug discovery that synthetic compounds may lack. Historically, a significant proportion of approved drugs have been derived from or inspired by natural products, particularly in areas like oncology, infectious diseases, and neuropharmacology. Their structural diversity enhances the likelihood of discovering novel mechanisms of action, making natural products a valuable reservoir for the development of new psychoactive agents. The study of these compounds, as depicted in stories, cartoons, and games, can help bridge traditional knowledge with modern pharmacological research, expanding the scope of drug discovery and fostering a deeper understanding of how these substances interact with biological systems.3,4

This article stands out for its innovative application of pharmacological mechanism analyses, complemented by advanced molecular modeling techniques. These tools will be used to explore the properties and hypothetical effects of the fictitious substances present in the selected works, providing a bridge between fiction and real scientific concepts. For example, molecular modeling will be employed to investigate the chemical structure of "magic potions" and "growth mushrooms", helping to elucidate the possible mechanisms of action of these substances in the human body, offering a unique perspective on how these fictional elements could interact with real biological systems.

In addition to increasing interest and understanding in Medicinal Chemistry, this approach highlights the role of creativity and interdisciplinarity in scientific education. The integration of popular culture in explaining pharmacological concepts not only facilitates student engagement but also demonstrates the applicability and relevance of Medicinal Chemistry in everyday and familiar contexts. Furthermore, this work significantly contributes to the field of Medicinal Chemistry by providing an innovative educational model, encouraging educators to inspire future generations of scientists and healthcare professionals.

By bridging fiction and scientific reality, our goal is to promote deeper engagement with Medicinal Chemistry, fostering an appreciation for its importance and potential in the real world. This article, therefore, not only opens new avenues for teaching complex concepts of Medicinal Chemistry but also sets a precedent for the use of innovative teaching methods in the field.

 

THE INTERSECTION OF MEDICINAL CHEMISTRY WITH POP CULTURE

Cultural representations of psychoactive substances in animations and games not only reflect public understanding of these compounds but can also influence scientific interest and research in Medicinal Chemistry. By exploring the scientific aspects underlying these representations, valuable insights can be gained into the relationship between public perception and scientific advancement.5

The intersection of Medicinal Chemistry with popular culture constitutes an interdisciplinary field of study that explores the manifestations and implications of scientific representation in non-academic contexts. This analysis aims to elucidate how Medicinal Chemistry is portrayed in popular culture and the effects of these representations on the public understanding and perception of science. Through a critical review of specific examples across various media, a reflection on the role of scientific accuracy in balancing the need for public engagement and entertainment is proposed.

Accuracy and dramatization on television: "Breaking Bad" as a case study

The series "Breaking Bad" created by Vince Gilligan, is often cited for its relatively accurate portrayal of chemical processes, specifically regarding the synthesis of methamphetamine.6 While the series enhances scientific accuracy, it intertwines these representations with deep dramatic narratives, exploring complex ethical themes. This balancing act illustrates the educational potential of media while highlighting the inherent ethical challenges in the practice of Medicinal Chemistry.7

Dystopian literature and pharmacological projections: analysis of "Brave New World"

"Brave New World" by Aldous Huxley anticipates ethical dilemmas associated with the development and use of chemical substances for behavioral control in a dystopian society. The work raises pertinent discussions on autonomy, consent, and the role of Pharmacology in modulating human experience, problematizing the instrumentalization of science for social control.5

Chemistry education through electronic games

The implementation of chemical concepts in electronic games, exemplified by "The Witcher" series, where potion crafting plays a central role, demonstrates how gamification can be used to spark interest in chemistry.8 In this series and game, alchemical environments are reported at various times, such as the one depicted in Figure 1. Although these elements are fictional, they introduce lay audiences to basic principles of component combination to achieve specific effects, suggesting the potential of electronic games as complementary educational tools in disseminating scientific knowledge.

 

 

Analysis of the intersection between Medicinal Chemistry and popular culture reveals a complex relationship, in which scientific accuracy and the need for engaging narratives often coexist in tension. The accurate representation of science holds the potential to educate and inspire the public, yet dramatization and oversimplification may perpetuate misunderstandings or stereotypes about scientific practice. Hence, there arises the necessity for a critical and reflective approach to how science is popularized, aiming not only for precision but also for ethical responsibility in constructing narratives about science accessible to the lay audience.

Studies10 have delved into how scientists perceive their interactions with news media, but few address their impressions of popular culture more broadly. To investigate this issue, researchers surveyed members of the Stem Cell Network Canada (SCN) to understand their views on popular representations of science and their perceived impact on public opinion, policies, and scientific conduct. A majority of respondents (57.1%) agreed that science is playing an increasingly important or prominent role in popular culture (such as movies, television, books, etc.). However, many expressed concerns about the accuracy of these representations. Almost none considered science portrayals to be accurate or highly accurate. In fact, the majority were at least somewhat skeptical of these representations, especially concerning specific topics such as cloning, the role of genetics in health, general stem cell research, induced pluripotent stem cell research, and the efficacy of unproven stem cell therapies offered abroad (sometimes referred to as "stem cell tourism").

To advance the analysis of representations of psychoactive substances in popular culture, the next sections of this article will detail interpretations of some emblematic works. In "Alice in Wonderland", we will explore the symbolism behind the magical potions that alter the protagonist's perception of reality. Next, we will examine the relationship between spinach consumption and superhuman strength in "Popeye", as well as the famous magic potion from "Asterix and Obelix" and its role in attributing extraordinary abilities. Additionally, we will analyze the magic mushrooms present in the "Mario Bros" game series and how they reflect human fascination with the pursuit of special powers. These detailed analyses will provide a deeper understanding of how popular culture portrays and interprets psychoactive substances, influencing our collective perception of science and entertainment. It is worth noting that these analyses are purely theoretical and are based on works of fiction. There is no direct correlation with real substances and their effects in the real world. Pharmacology is a complex field that studies the precise and often predictable effects of chemical substances on the body, something that Alice's adventures only address in a fantastical and imaginative way.

 

ALICE IN WONDERLAND: A PSYCHEDELIC JOURNEY THROUGH MEDICINAL CHEMISTRY AND BEYOND

"Alice in Wonderland",11 a timeless work by Lewis Carroll, provides a unique journey that transcends the physical world, exploring not only psychedelic representations but also advanced concepts of Medicinal Chemistry, Pharmacology, Drug Delivery, and Health Sciences that can be unearthed beneath the surface of the story. The mushroom symbolized in the story contains psilocybin, a prodrug that, upon ingestion, is converted into psilocin in the body. Psilocin primarily acts as an agonist on serotonin receptors, especially the 5-HT2A subtypes, present in the prefrontal cortex (Figure 2). This interaction triggers neuronal activity modifications that translate into profound perceptual alterations, including visual distortions, changes in time perception, and states of expanded consciousness.13

 

 

The study of the Pharmacology of psilocybin reveals complex nuances in the modulation of the serotonergic system (Figure 3). Contemporary research highlights psilocybin's ability to modulate brain connectivity, especially in the default mode network (DMN), resulting in unique subjective experiences and intensified introspection. This modulation occurs primarily through its interaction with serotonin receptors, particularly the 5-HT2AR subtype, located on postsynaptic neurons within the brain. Psilocybin's actions on these receptors disrupt the typical functioning of serotonin neurotransmission pathways, altering the flow of information in the brain and leading to the characteristic effects observed during psychedelic experiences. Understanding these interactions sheds light on the intricate interplay between psilocybin and the serotonergic system, providing insight into both its therapeutic potential and its impact on subjective consciousness.15 Understanding these pharmacological mechanisms not only sheds light on potential therapeutic effects but also challenges paradigms in neuropharmacological research.

 

 

The efficient delivery of psilocybin by the organism is a complex dance between the mushroom's mycelial formulation and the host's physiological response. The mycelial matrix not only protects the molecule during passage through the gastrointestinal tract but also favors its effective absorption. Detailed understanding of the interaction between the mycelial structure and human physiology can inspire advances in Drug Delivery strategies. Exploring how these mushrooms naturally optimize the delivery of active compounds opens doors to designing more effective and specific Drug Delivery systems.16 In the intricate landscape of psilocybin Pharmacology, understanding its journey within the human body is crucial. As psilocybin embarks on its path, it encounters a complex interplay between the mushroom's mycelial formulation and the intricacies of human physiology.17

This interaction governs the efficient delivery of psilocybin, balancing protection during gastrointestinal transit with optimal absorption. However, the story does not end there. Within the human nervous system, psilocybin engages in a detailed biochemical dance, alongside its active metabolite psilocin.18 Here, the intricate machinery of neurotransmitter pathways comes into play, particularly serotonin signaling, where psilocin exerts its influence. To provide a visual aid to this biochemical narrative, Figure 4 illustrates a detailed biochemical pathway involving psilocin and psilocybin within the human nervous system. This figure sheds light on the transformation of tryptophan into serotonin, highlighting the role of psilocin in selectively binding to serotonin receptors, thus influencing neurotransmitter signaling. Through this illustration, we gain a deeper understanding of the intricate biochemical interactions underlying psilocybin's effects on the human nervous system.

 

 

A deep dive into Carroll's work also allows for fruitful dialogue with the Health Sciences. Alice's incessant questioning about the nature of reality, her altered perception, and the quest for truth underlying the apparent absurdity of Wonderland resonate with contemporary investigations into altered states of consciousness.

Pharmacological analysis of psilocybin not only expands our understanding of its effects on the brain but also underscores the importance of these substances in exploring the limits of consciousness and in the pursuit of innovative mental health therapies.20

"Alice in Wonderland" not only reveals the wonder of the psychedelic but also serves as a microcosm for exploring the frontiers of Pharmacology and Health Sciences. The interaction between psilocybin and serotonin receptors, the intricate Drug Delivery mechanisms present in mushrooms, and Alice's existential reflections converge, creating a fascinating mirror between fiction and science.21 This is an invitation to explore the wonders of both imagination and scientific research.

The pharmacological analysis of the book "Alice in Wonderland" can be fascinating, considering the various mysterious substances Alice encounters and the peculiar effects they have on her. Although the book is a work of fantasy, we can speculate on the pharmacological mechanisms behind Alice's transformations and bizarre experiences using real principles of Pharmacology.22 It is important to note, however, that these speculations are purely academic and for entertainment purposes, given the fictional context of the book.

Size alteration (growth and shrinking)

Substance: "Eat me" and "Drink me". In the history, Alice encounters a bottle labeled "Drink me" that makes her shrink and a cake labeled "Eat me" that makes her grow.

Speculative pharmacological mechanism: one could hypothesize that the "Drink me" potion contains substances that function similarly to ion channel modulators, temporarily modifying the permeability of the cell membrane to specific ions, resulting in rapid cell volume loss.23 Conversely, the "Eat me" cake might include growth factors or anabolic substances that promote protein synthesis and cellular growth.

Perception and reality alterations

Substance: mushrooms. Alice consumes parts of a mushroom that cause her to alternate between growing and shrinking.

Speculative pharmacological mechanism: the mushrooms could contain hallucinogens, substances that alter perception, thought, and consciousness, similar to psilocybin found in certain real psychoactive mushrooms.24 These compounds primarily act through the activation of the serotonin 5-HT2A receptor in the brain, which can lead to altered reality experiences.

Increase in energy and motivation

Substance: not specified in the book, but one could speculate about drinks or edibles that give Alice or other characters' additional energy or motivation.

Speculative pharmacological mechanism: stimulant substances, such as caffeine or amphetamines, increase central nervous system activity, potentially temporarily increasing energy and motivation. They act by increasing the release of neurotransmitters such as dopamine and norepinephrine.25

 

POPEYE: EXPLORING THE BIOACTIVE COMPONENTS OF SPINACH

"Popeye the Sailor" is a pop culture icon, and its association with spinach consumption is legendary. The bioactive components of spinach, its pharmacological representation and health implications can be explored, delving into aspects of Medicinal Chemistry, Pharmacology and Health Sciences.24

The almost instantaneous effect of spinach consumption on Popeye's strength harks back to the presence of nitrates in this vegetable. "Nitrites in spinach convert to nitric oxide in the body, promoting vasodilation. Spinach is particularly rich in nitrate, which is converted into nitric oxide, increasing blood flow and enhancing oxygen and nutrient delivery to muscles. This effect potentially boosts muscular strength by improving tissue oxygenation and nutrient supply (Figure 5)".27,28 The focus on vasodilation highlights the crucial role of spinach in promoting cardiovascular health, a significant area of research in Health Sciences. Ecdysterone is a type of steroid hormone found in plants, including spinach and has been extensively studied for its potential anabolic effects. Some studies suggest that ecdysterone may increase muscle protein synthesis and enhance physical performance, leading to its popularity as a possible supplement for athletes and bodybuilders. The benefits of ecdysterone for the human body and cells are detailed in scientific reports.29

 

 

In addition to nitric oxide, spinach is a rich source of antioxidants, fiber, vitamins, and minerals. These bioactive compounds offer a variety of health benefits, from protection against oxidative stress to the promotion of ocular and bone health.30

Antioxidants: spinach is rich in phenolic compounds such as lutein, kaempferol, zeaxanthin, and quercetin, which possess antioxidant and anti-inflammatory properties. These antioxidants help combat premature skin aging and protect against cardiovascular diseases.31

Vitamins: spinach is an excellent source of vitamins A, C, and E. These vitamins are essential for eye health, maintenance of cell membranes, and prevention of vision problems such as macular degeneration.

Minerals: spinach contains important minerals such as potassium, calcium, iron, and magnesium. Potassium helps regulate blood pressure, while iron is crucial for preventing anemia. Additionally, calcium is essential for bone health.

Fiber: spinach has a high fiber content, which contributes to digestive health and helps maintain a healthy gastrointestinal system.

The pharmacological analysis of spinach extends beyond the comic aspect of comic books, providing a more comprehensive perspective on the positive effects of these compounds on human health. The portrayal of Popeye as a justice defender strengthened by spinach highlights the connection between nutrition and health. This narrative reflects the fundamental principles of phytotherapy, where natural compounds from foods are used to promote health and prevent diseases. Exploring this connection not only enriches Popeye's narrative but also underscores the importance of healthy food choices in promoting well-being.

Analyzing spinach through the lens of Health Sciences reveals a range of beneficial properties. In addition to vasodilatory effects, the bioactive compounds in spinach have been associated with reducing the risk of chronic diseases such as cardiovascular diseases and certain types of cancer. The interdisciplinarity between Pharmacology, nutrition, and preventive medicine unveils the secrets of spinach, transforming it from a mere fictional food into a tangible example of the interconnection between nutrition and health.

The saga of spinach in Popeye's story transcends entertainment, becoming a lesson in Health Sciences. In-depth analysis reveals the complexity of the bioactive compounds present in this vegetable and highlights how food choices can have direct impacts on human health. Popeye's portrayal not only inspires laughter but also invites reflection on the importance of a balanced diet and its long-term beneficial effects.

The pharmacological analysis of the character Popeye and his iconic consumption of spinach to gain immediate strength is an interesting example of how popular culture can reflect (and exaggerate) real concepts of nutrition and Pharmacology. Unlike Alice in Wonderland or the Mario Bros universe, Popeye's case has a more direct parallel with reality, even though the dramatic effect is purely fictional.

Spinach-immediate effect

Speculative pharmacological mechanism: the instantaneous effect of spinach on Popeye is purely fictional. However, if we were to speculate on a mechanism by which a food could provide an immediate boost, we could consider the rapid absorption of simple carbohydrates for a sudden energy increase or the ingestion of stimulating substances that act on the central nervous system, enhancing attention and muscular response. Naturally, no food provides effects as dramatic and immediate as those seen in the cartoon.

Super strength as a defense or attack mechanism

Speculative pharmacological mechanism: in reality, muscular strength and endurance can be increased in the long term through a diet rich in certain nutrients (such as proteins and nitrates) and physical training. Spinach may contribute to muscular health and recovery after exercise due to its nutritional profile, but not instantly or miraculously as depicted in the cartoon.

While Popeye's instant strength increase after consuming spinach is fictional, the cartoon highlights the importance of a nutrient-rich diet for health and physical performance. The idea that specific foods can have beneficial effects on strength and health is valid, but the real effects are cumulative and result from consistent consumption and a healthy lifestyle, rather than an instant transformation.

 

MARIO BROS: EXPLORING MUSHROOM POWERS FROM THE PERSPECTIVE OF HEALTH, BIOLOGY, AND MEDICINAL CHEMISTRY

The journey of Mario and Luigi through the Mushroom Kingdom is not just a quest for adventure but also an exploration of bioactive elements and potential health benefits associated with mushrooms. It is possible to delve into the warp pipes of the mushroom world in the Mario Bros universe and examine aspects of Medicinal Chemistry, Pharmacology, Biology and Health Sciences.

The iconic Super Mushrooms, which grant Mario and Luigi superhuman abilities, may have an intriguing biological basis. Ergosterol, a precursor to vitamin D2, is found in mushrooms and, when exposed to sunlight, can be converted into vitamin D2. Vitamin D is essential for bone and immune health and obtaining it from mushrooms highlights a potential nutritional approach to optimizing health.32 Furthermore, analyzing specific compounds derived from ergosterol from the perspective of Medicinal Chemistry may reveal potential therapeutic targets and contribute to the research of new drugs. In addition to Super Mushrooms, the Mario Bros universe features Shrooms, representations of common mushrooms. Exploring this facet, we highlight the presence of bioactive substances in mushrooms, such as beta-glucans, selenium, and potassium (Figure 6), which have been associated with immunomodulatory and antioxidant benefits.34 Mushrooms also contain ergosterol, which can be converted to vitamin D2 (ergocalciferol) upon exposure to UV light. Vitamin D2 is an important form of vitamin D, especially in fungi and yeast. In contrast, vitamin D3 (cholecalciferol), typically produced in the skin in response to sunlight, is the form of vitamin D more commonly found in animal sources. Both vitamins D2 and D3 are crucial for maintaining bone health and supporting the immune system, but they differ in their sources and the way they are processed in the body.

 

 

Mushrooms, pivotal in the Mario Bros universe, offer a lesson in biology. By exploring the different types of mushrooms present in the game, from those that provide growth to those that confer special abilities, an educational opportunity arises to understand the biological diversity of these organisms. A detailed analysis of mushroom biology not only reinforces fundamental biology concepts but also highlights the importance of biodiversity for ecosystem health.

Investigating the Medicinal Chemistry of mushrooms opens a promising field. Compounds such as triterpenes, polysaccharides, and sterols found in mushrooms have demonstrated diverse pharmacological activities, including anti-inflammatory, anticancer, and immunomodulatory properties.35 Delving deeper into the molecular analysis of these compounds may reveal not only new therapeutic agents but also insights into the interaction between natural molecules and biological processes.

Analyzing mushrooms in the context of Health Sciences highlights their nutritional relevance and potential health benefits. Besides being a source of ergosterol and vitamin D, mushrooms offer proteins, fibers, and a variety of micronutrients. Exploring how these elements can be incorporated into a balanced diet underscores mushrooms as allies in health promotion, also highlighting the importance of dietary diversification.

The journey of Mario and Luigi through the Mushroom Kingdom transcends mere entertainment, providing a unique educational platform. In-depth analysis not only reveals correlations with real biological elements but also underscores the ability of game narratives to teach engagingly and playfully. Jumping into an integrated understanding, the saga of mushrooms in Mario Bros becomes not just a virtual adventure but an opportunity to explore the links between fiction, biology, Medicinal Chemistry, and health.

Analyzing Pharmacology within the Mario Bros universe is an intriguing task, given the presence of various items that alter characters' abilities and physical characteristics in fantastic ways. Let's speculate on the pharmacological mechanisms behind some iconic items in the Mario Bros universe, always remembering that this is a purely fictional interpretation for entertainment purposes.

While these associations are made based on the real properties of mushrooms, it is important to emphasize that the effects portrayed in the games are purely fictional and should not be interpreted as scientifically accurate. Game developers often take creative liberties to make gameplay more interesting and engaging.

Growth mushrooms

Item: red mushrooms that make Mario grow.

Speculative pharmacological mechanism: the growth mushrooms in the Super Mario Bros universe, notably represented by the iconic red mushroom, are directly linked to Amanita muscaria, a mushroom species containing psychoactive molecules. From a biochemical standpoint, these mushrooms carry isoxazoles, including substances like ibotenic acid and muscimol, which serve as the primary psychoactive agents responsible for psychedelic effects upon ingestion.36,37 Ibotenic acid acts as an agonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, while muscimol functions as a gamma-aminobutyric acid (GABA) agonist, affecting GABA A receptors (Figure 7).39 Additionally, the presence of muscarine and tropane alkaloids in Amanita may contribute to the observed effects in the Super Mario Bros, given the impact of these substances on the nervous system.40

 

 

The combination of these molecules even accounts for the unique experience of growth and slowness associated with the growth mushrooms in the Super Mario Bros world, directly tied to the visual and auditory esthesia, space and time distortion effects of Amanita.41 This provides a captivating biochemical perspective on these popular elements in pop culture.

Fire flower

Item: a flower that allows Mario to shoot fireballs.

Speculative pharmacological mechanism: it could be speculated that the Fire Flower contains a substance that induces the production of some type of bioenergy or biofuel, metabolized rapidly and released in a controlled manner through the hands. This mechanism could involve the activation of specific biochemical pathways that increase the oxidation of chemicals with energy release.42

Starman

Item: a star that temporarily makes Mario invincible.

Speculative pharmacological mechanism: this effect could be likened to substances that cause a sudden surge in adrenaline levels, increasing physical endurance and pain tolerance. "Invincibility" would be the result of an extreme increase in the body's fight or flight response, temporarily reducing the sensation of pain and enhancing physical capacity.43

Poisonous mushrooms

Item: mushrooms that harm or shrink Mario when touched.

Speculative pharmacological mechanism: these mushrooms could release toxins that, when absorbed by Mario's body, interfere with normal metabolic pathways, causing cellular damage or inhibiting the synthesis of proteins necessary for maintaining cell size and function.44

These explanations are, of course, speculative and tailored to the context of a video game universe, where fantasy prevails over the known laws of Pharmacology and biology. In the real world, the effects of chemical substances on the body are studied rigorously and in detail, following scientific principles that do not allow for such fantastical transformations.

 

ASTERIX AND OBELIX: THE MAGIC POTION AND THE SECRETS OF MEDICINAL CHEMISTRY IN THE GAULISH VILLAGE

The Magic Potion is the central element in the saga of Asterix and Obelix, granting the Gauls formidable strength. From a pharmacological standpoint, this unique mixture can be seen as an ergogenic compound, capable of significantly enhancing the physical capacity of those who consume it. The composition of the potion remains a mystery, but the idea of an elixir that provides superhuman strength suggests the possibility of a specific interaction with muscular or metabolic systems.45 Panoramix's relentless quest for the secret ingredient underscores the narrative of research and discovery, while the prohibition of its use by other communities highlights the potential dangers associated with this substance, contributing to a broader discussion on ethics and responsibility in the use of substances with enhanced potential.

Panoramix, in his role as an alchemist, transcends the stigma of the typical wizard. His ability to manipulate natural ingredients and create a compound that defies physical limits highlights the interconnection between botanical knowledge and pharmacological skills. A deeper analysis of the Magic Potion from a pharmacological perspective not only adds complexity to the plot but also offers an intriguing opportunity to explore the ethical and social implications of interventions that alter strength and physical capacity.46

The Gaulish village essentially becomes a natural pharmacy under the guidance of the druid Panoramix. The meticulous collection of specific plants and herbs highlights the importance of understanding the unique properties of each ingredient. Through the lens of Medicinal Chemistry, this practice reveals the ancestral wisdom of identifying bioactive compounds and understanding how different substances can interact to create synergistic effects. Panoramix's ability to create a potion with such extraordinary effects underscores not only his profound understanding of nature but also his mastery in the art of formulation.47

Exploring Medicinal Chemistry behind the specific choice of plants and herbs for the Magic Potion opens doors to a discussion on the practical application of botanical knowledge in traditional medicine. Each ingredient may represent not only a source of physical strength but also contain bioactive compounds with medicinal properties. This highlights the importance of biodiversity in the search for therapeutic substances and the need to understand the complex interactions between different botanical compounds.48

The biological approach to Gaulish strength is not limited solely to muscle building but also involves a deeper analysis of hormonal and metabolic responses. Exploring how the Magic Potion may influence these biological processes adds layers of complexity to the narrative, highlighting implications not only for immediate physical performance but also for the overall health of the characters.49 The saga of Asterix and Obelix, therefore, provides a unique opportunity for reflections on the subtle interactions between natural compounds and biological systems, fostering a deeper appreciation of Biology as a dynamic and interconnected science.

"Asterix and Obelix" not only offers entertainment but also provides intriguing lessons at the intersection of fiction and science. A thorough analysis of the Magic Potion reveals aspects of Medicinal Chemistry, Pharmacology, Biology, and Health Sciences, highlighting the wealth of knowledge that can be drawn from fictional narratives. The Gauls' saga is not just a comic adventure but also a fascinating exploration of the secrets behind strength and health in the Gaulish Village. By connecting scientific disciplines to the narrative, the story of Asterix and Obelix serves as a bridge between imagination and knowledge, inspiring deeper reflections on the mysteries of nature and the possibilities of practical applications of scientific concepts.

The comic book series "Asterix and Obelix" created by René Goscinny and Albert Uderzo, presents an interesting premise that lends itself to creative pharmacological analysis. The protagonists, Asterix and Obelix, are two Gaulish warriors who fight against the Romans with the help of a magic potion prepared by the druid Panoramix. This potion grants temporary superhuman strength to those who drink it. Obelix, who fell into the potion cauldron as a baby, has a permanent effect from the potion, making him unusually strong all the time.

Magic potion

Item: magic potion that grants superhuman strength.

Speculative pharmacological mechanism: the potion could be analyzed similarly to some ergogenic structures, such as creatine, hGH, and amphetamines, which can increase the body's energy production capacity and improve physical performance. It could, theoretically, enhance the synthesis of ATP (adenosine triphosphate), which is the primary source of energy for muscle contractions (Figure 8). Alternatively, the potion could act as a potent central nervous system stimulant, increasing the release of catecholamines (such as adrenaline and noradrenaline), which in turn enhance muscle strength and endurance temporarily.50

 

 

Permanent effect on Obelix

Speculative pharmacological mechanism: Obelix's case, where he has a permanent effect from the potion due to exposure during childhood, is a fictional example with no direct parallel in Pharmacology. However, it could be speculated that early exposure resulted in a permanent alteration in Obelix's metabolism or in genetic expression related to muscle development and mitochondrial function, leading to lasting enhanced muscle capacity.

Superhuman strength

Speculative pharmacological mechanism: the superhuman strength depicted in the comics could theoretically be attributed to an increase in the efficiency of recruiting type II muscle fibers (fast-twitch fibers), maximizing muscle strength and contraction speed. Additionally, the potion could increase resistance to muscle damage and accelerate recovery, allowing characters to maintain their exceptional strength with less fatigue.51

In reality, enhancing physical performance is a complex field involving nutrition, training, genetics, and sometimes Pharmacology, but always within the bounds of what is safe and ethically acceptable.

Integrating the exploration of speculative pharmacological mechanisms with the molecular docking investigation of psychoactive substances offers a fascinating glimpse into the intersection of scientific inquiry and fictional narratives. While the preceding discussion delved into theoretical frameworks surrounding superhuman strength depicted in comics, it is essential to ground the exploration within the realm of scientific reality. Enhancing physical performance is indeed a multifaceted endeavor, encompassing factors such as nutrition, training methodologies, genetic predispositions, and, occasionally, pharmacological interventions. However, any such interventions must adhere to stringent safety and ethical standards. This sets the stage for a deeper dive into the molecular interactions of psilocin and muscimol, key psychoactive components found in Psilocybe cubensis and Amanita muscaria, respectively. Through molecular docking simulations, researchers aim to elucidate the potential binding modes and affinities of these compounds, shedding light on their pharmacological effects within the context of well-defined protein targets.

 

DOCKING INVESTIGATION OF PSILOCIN (P. Cubensis, ALICE IN WONDERLAND) AND MUSCIMOL (A. Muscaria, MARIO BROS)

Seeking to evaluate the modes of interaction of the main psychoactive substances in this work, psilocin (metabolic product of psilocybin, present in P. cubensis) and muscimol (metabolic product of ibotenic acid, present in A. muscaria) were selected to carry out molecular docking. For psilocin, based on the method of Radan et al.,52 GOLD software (v. 2023.2.0)53 was used with the 5-HT2A receptor (PDB ID: 7RAN) in physiological pH (7.4) for protein and ligand. The protein was pre-optimized using PARSE force field, while the ligand was pre-optimized using MMFF94.54 The spherical cavity was generated with 8.0 Å from the cocrystallized ligand ((3R)-3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,3,6-tetrahydropyridin-1-ium; PDB ID: 3IQ) and the scoring function used was ChemPLP (Piecewise Linear Potential). One hundred poses were generated.

For muscimol, the muscarinic acetylcholine receptor (PDB ID: 5CXV) was used due to its response to muscarine. As muscimol also has a five-membered heterocycle with a hydroxyl and a cationic nitrogenous fraction, the structural similarity is significant. As the 5CXV crystal was obtained bound to antagonist and muscimol is an agonist, blind docking was performed using a deep learning diffusion model through DiffDock (Figure 9). The aim was verifying whether the active site remained the same. The ligand was set at physiological pH (7.4), being compared with the result obtained for psilocin.

 

 

For redocking, GOLD software showed a root mean square deviation (RMSD) of 1.2912 Å relative to the cocrystallized ligand (3IQ), demonstrating validation of the method. The highest score was obtained for pose 82 (50.57). Psilocin showed hydrogen bond, π-Sigma, and hydrophobic types as main interactions. The highest pose being 81, with a score of 52.69 (Figures 9a and 9b).

Muscimol, on the other hand, presented π-cation type interaction, because the cationic region of the ligand was approximately 4 Å away from the phenolic group. Hydrogen bonds were found in both ligands, as both have nitrogenous cationic groups at physiological pH. The hydrophobic interactions were carried out by the amino acid residues Phe340 and Val156 for psilocin and Tyr106 for muscimol. While in muscimol the π-π interactions observed were stacked, with psilocin it was T-shaped, due to the spatial orientation of the phenylalanine aromatic ring (Figures 9c and 9d).

As both proteins are transmembrane receptors coupled to G proteins and present 7 α-helices characteristic of transmembrane domains, it was possible to align them and observe whether the blind docking active site for muscimol (muscarinic receptor) was in accordance with the same active site of psilocin (5-HT2A), which was validated through redocking with the cocrystallized ligand. It was observed that the diffusion blind docking model presented the similar bound mode presented by electron microscopy of 5-HT2A (PDB ID: 7RAN) and by muscarinic acetylcholine receptor bound to antagonist (PDB ID: 5CXV), which suggests that the agonist interacts in a similar region (Figure 10, RMSD = 2.41 Å).

 

 

ETHICAL AND SOCIAL IMPLICATIONS IN THE USE OF PSYCHOACTIVE SUBSTANCES IN ANIMATIONS AND GAMES

The portrayal of psychoactive substances in animations and games is not just a matter of scientific accuracy or education in Medicinal Chemistry; it also raises important ethical and social questions. These representations have the potential to influence perceptions, attitudes, and behaviors regarding drug use, especially in younger and more impressionable audiences. In this section, we will discuss the ethical and social implications of these representations, addressing the responsibility of content creators, drug education, and promoting a balanced understanding of psychoactive substance use.

Creators of animations and games often operate in a rich creative territory where fantasy and reality intertwine. While creative freedom is a fundamental value in these media, there is an inherent responsibility in representing themes related to psychoactive substances. The way these substances are portrayed can reinforce stereotypes, misinformation, or glamorous perceptions of drug use, potentially downplaying the real risks associated with their consumption.55 For example, glorifying drugs as a source of superhuman powers or magical solutions to complex problems can convey misleading messages, especially to younger audiences.

The presence of psychoactive substances in popular content also underscores the importance of drug education, which should be comprehensive, evidence-based, and tailored to different age groups. Effective drug education should go beyond simple "just say no" approaches, incorporating an understanding of pharmacological effects, health risks, and the legal and social implications of drug use.56 Additionally, it is crucial that this education promotes critical thinking, enabling young people to make informed and responsible choices about substance use.

To promote a balanced understanding of psychoactive substance use, it is essential to balance the representation of their negative effects and therapeutic potential. While some animations and games may portray psychoactive substances in a playful or fantastical manner, it is important to contextualize these representations with accurate information about the real effects of these substances. For example, discussing the potential therapeutic benefits of certain drugs, such as psychedelics in psychotherapy, should be balanced with discussions about the risks of abuse and dependence.57

The representations of psychoactive substances in animations and games are a point of intersection between entertainment, education, and ethics. The responsibility of content creators, combined with efforts in drug education and the promotion of a balanced understanding, can help shape healthy and informed perceptions about psychoactive substance use. By addressing these issues responsibly and informatively, animations and games not only entertain but also contribute to social and individual well-being.

 

STRATEGIES FOR RESPONSIBLE AND EDUCATIONAL REPRESENTATION

The portrayal of psychoactive substances in animations and games, while being a source of entertainment, carries with it the power to influence perceptions and behaviors. To navigate the complexities associated with these representations, it is essential to adopt strategies that promote a responsible and educational approach. In this section, we will explore effective strategies that can be employed by content creators, educators, and society at large to ensure that representations of psychoactive substances positively contribute to the knowledge and well-being of the public.

Education of content creators

Content creators should be encouraged to acquire a solid understanding of the effects, risks, and social contexts associated with the psychoactive substances they choose to portray. Workshops, seminars, and educational resources can provide creators with the necessary information to represent these substances accurately and responsibly. Additionally, collaboration with experts in Medicinal Chemistry, psychology, and public health can enrich the content, ensuring that the representations are informed and evidence-based.

Incorporation of educational messages

Animations and games have the potential to include educational messages subtly and seamlessly, informing viewers about the effects and risks of psychoactive substances without compromising the quality of entertainment. Strategies include using characters that face realistic consequences for misuse of substances, or that demonstrate responsible behavior regarding drugs. Additionally, supplementary materials such as discussion guides and Q&A sessions can be provided to foster dialogue and reflection among the audience.

Partnerships with health organizations

Content creators can benefit from partnerships with health and education organizations to ensure that representations of psychoactive substances are accurate and convey positive messages. These organizations can offer expertise and validate health-related content, ensuring that it aligns with recommended practices for drug prevention and education. Joint awareness campaigns can also be an effective strategy to amplify the educational impact of these representations.

Feedback and dialogue with the public

Interaction with the public can offer valuable insights into how representations of psychoactive substances are perceived and the effects they have on viewers. Content creators and distributors can use polls, discussion forums, and social media to collect feedback and engage in constructive dialogues on the topic. This approach can not only help adjust future representations to be more informative and responsible but also promote a closer and more trusting relationship with the audience.

Fostering critique and analytical thinking

Classroom discussions about representations of psychoactive substances can address not only the scientific aspects but also the social, historical, and ethical contexts related to the use of these substances.

Development of interactive educational tools

Creating interactive educational tools, such as educational games, can offer an engaging approach to conveying information about psychoactive substances. These tools can simulate the effects of drugs realistically, highlighting the risks and consequences of misuse. By making learning about psychoactive substances an interactive experience, these tools have the potential to captivate the audience in an educational and memorable way.

Facilitated access to scientific resources

Making scientific resources accessible to the public, such as articles, explanatory videos, and infographics, can play a crucial role in promoting education about psychoactive substances. Content creators can include links or references to these resources in their productions, encouraging the audience to explore more detailed information on the topics covered. This not only enriches the viewer's experience but also empowers the public to seek knowledge autonomously.

Encouraging narrative diversity

When portraying psychoactive substances, it is essential to recognize the diversity of experiences and perspectives. Content creators can explore narratives that go beyond traditional stereotypes, incorporating stories that reflect different cultural, social, and individual contexts related to substance use. This not only enriches the representation but also contributes to a more comprehensive and inclusive understanding of the impact of psychoactive substances on society.

By adopting these strategies, the representation of psychoactive substances in animations and games can evolve into an educational and responsible space, contributing to the development of a more informed and conscious audience. These practices not only benefit the public but also promote integrity and ethics in content creation, setting positive standards for the entertainment industry.

 

INTERSECTION BETWEEN POP CULTURE, NATURAL SUBSTANCES AND MEDICINAL CHEMISTRY RESEARCH: A MULTIDISCIPLINARY ANALYSIS

The intersection of natural substances, iconic fictional characters, and the popular fascination with superfoods creates a vast and inspiring field for research in Medicinal Chemistry. In this multifaceted scenario, characters like Popeye, Mario Bros, Alice in Wonderland, and Asterix and Obelix play interesting roles in interacting with natural substances such as ecdysterone,58 fueling the public's imagination and providing a platform for health education and scientific innovation.

Inspiration for research

Discovery of new compounds

The notoriety of characters like Mario Bros and Popeye may stimulate researchers to delve deeper into the properties of natural substances found in foods, such as mushrooms and spinach, seeking to discover new compounds with therapeutic potential.

Biotechnology and metabolic engineering

The narrative of Asterix and Obelix, with its creative use of plant-based magic potions, could inspire research in biotechnology and metabolic engineering aimed at enhancing and synthesizing beneficial compounds.

Development of new medications

Synthetic analogs

Medicinal Chemistry can leverage the chemical structures found in natural substances associated with these characters, such as the plants Alice encounters in her Wonderland, to develop synthetic analogs with enhanced therapeutic properties.

Pharmacognosy

Studying the substances present in "magical" foods of characters like Popeye may lead to valuable discoveries for the development of medications from natural sources.

Education and health promotion

Nutrition and public health

Characters like Popeye, who gain strength from eating spinach, can be used to promote nutrition and public health. Integrating these figures into educational campaigns can encourage healthier dietary choices.

Demystification of myths

Scientific knowledge can help debunk myths, such as the supposed magical power of potions from Asterix and Obelix, providing a realistic understanding of the benefits and limitations of foods and substances associated with these characters.

Interdisciplinary collaborations

Science, culture, and society

Interdisciplinary collaboration among science, popular culture, and health can be expanded, involving not only scientists but also content creators, educators, and health professionals, pooling efforts to promote understanding and application of natural therapeutic approaches.

In summary, the fusion of natural substances, beloved fictional characters, and the popular appeal of superfoods creates fertile ground for advances in Medicinal Chemistry. By incorporating elements of engaging narratives found in Mario Bros, Alice in Wonderland, and Asterix and Obelix, we can not only inspire research but also promote public awareness and understanding of the science behind our favorite foods and supplements.

 

CONCLUSIONS

This study delves into the portrayal of psychoactive substances within popular culture, particularly focusing on their depiction in cartoons and games, employing the framework of Medicinal Chemistry. Through our analysis, we explore the process by which these intricate substances, with their nuanced compositions and effects, are distilled and reshaped to fit within fictional narratives, ultimately influencing public perceptions of scientific concepts. By examining iconic examples like "Alice in Wonderland", "Mario Bros", "Popeye", and "Asterix and Obelix", we not only scrutinize the interpretation of science but also delve into how it is reimagined as narrative elements, sparking imagination and molding cultural outlooks.

Additionally, this research addresses a notable gap in existing literature by presenting a multidisciplinary approach that amalgamates principles of Medicinal Chemistry with media scrutiny and molecular modeling. Notably, in this article, unprecedented discussions involving molecular docking were conducted, offering novel insights into the potential interactions of psychoactive substances with biological targets. By incorporating these innovative methodologies and analyses, we not only deepen our comprehension of how psychoactive substances are portrayed in popular media but also offer valuable insights for advancing research in Medicinal Chemistry and the development of future pharmacological treatments.

Through emphasizing the significance of public science communication and fostering media literacy, this study contributes to nurturing critical thinking and fostering a more comprehensive understanding of the dynamic interplay between science, popular culture, and entertainment.

 

ACKNOWLEDGMENTS

The authors are highly thankful to Universidade Federal de Santa Catarina (UFSC) and Universidade Federal Fluminense (UFF). V. N. thanks the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, V. N. 310656/2021-4) and Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro (E-26/202.911/2019, E-26/210.325/2022 and E-26/200.235/2023) for the financial support.

 

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Editor handled this article: Jorge M. David

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