Mini reviews in medicinal chemistry最新文献

{"title":"Insight into the Advancement of Synthesis and Biological Activity of Pyridine and Its Derivatives: A Review.","authors":"Ayush Jain, Chandana Majee, Sadhana Sharma, Rupa Mazumder","doi":"10.2174/0113895575423489260115064548","DOIUrl":"https://doi.org/10.2174/0113895575423489260115064548","url":null,"abstract":"<p><strong>Introduction: </strong>Pyridine is an organic compound consisting of a six-membered ring containing one nitrogen atom. While it is frequently used as a solvent in organic laboratories, pyridine derivatives have varied applications in functional nanomaterials, act as essential ligands in organometallic compounds, and play a role in asymmetric synthesis catalysis.</p><p><strong>Materials and methods: </strong>Pyridine's varied reactivity makes it an essential building block in organic synthesis, with its derivatives showing encouraging pharmacological effects. This study includes a thorough review of the literature, critical analysis, and synthesis of current research. It encompasses the growing body of chemical knowledge and holds important implications for drug development.</p><p><strong>Results: </strong>This review provides a comprehensive overview of the various synthetic approaches for creating pyridine derivatives, highlighting different schemes and methods used in their synthesis. Additionally, it succinctly explores the biological activities associated with pyridine and its derivatives, offering insights into their significance in medicinal chemistry. The biological activities associated with pyridine derivatives showcase their versatile pharmacological potential.</p><p><strong>Discussion: </strong>Pyridine-containing compounds are important pharmacophores in a number of commercially available medications, and advanced synthesis of pyridine derivatives demonstrates increased efficacy and decreased toxicity in the context of drug discovery.Notwithstanding these developments, there are still problems, such as those pertaining to metabolic stability, selectivity, and possible off-target effects.</p><p><strong>Conclusion: </strong>This review underscores the critical need for ongoing research into the different synthetic methods for producing pyridine derivatives. Such advancements are essential for paving the way toward the development of novel and more effective therapeutic agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond a Psychotropic Plant: Exploring the Ethnomedicinal Value of Anadenanthera colubrina var. cebil.","authors":"Romina Belen González, Gonzalo Adrián Ojeda, Ana Melissa González Miragliotta, Gabriela Ana Leticia Ricciardi, Ignacio Carrera, Ana María Torres, Eduardo Dellacassa","doi":"10.2174/0113895575418590260116110240","DOIUrl":"https://doi.org/10.2174/0113895575418590260116110240","url":null,"abstract":"<p><p>Anadenanthera colubrina var. cebil (Griseb.) is an ecologically adaptable species native to South America, thriving across a variety of ecosystems, including the dry forests and savannas of Brazil, Argentina, Paraguay, and Bolivia, as well as the Andean highlands of Peru and Chile. Beyond its ecological significance, A. colubrina var. cebil is noted for its traditional use in ethnomedicine and for its diverse pharmacological activities reported in the scientific literature. Indigenous communities (Guaraní, Tupí, and Wichi) have long integrated this species into their healthcare and ritual healing practices, using it in ceremonial, medicinal, and shamanic purposes. Applications include the use of plants in psychoactive rituals and in the treatment of respiratory conditions, inflammation, and various infections. The ethnomedicinal diversity associated with A. colubrina var. cebil has been attributed to its phytochemical profile, including alkaloids such as bufotenine (5-hydroxy-N, N-dimethyltryptamine, 5- OH-DMT), N, N-dimethyltryptamine (DMT), and 5-methoxy-N, N-dimethyltryptamine (5-MeODMT), triterpenes, steroids, saponins, and flavonoids (quercetin, anadanthoflavone). Preclinical research has confirmed a wide spectrum of pharmacological properties, particularly in extracts of the bark and leaves. Activities reported include anti-inflammatory, antinociceptive, antimicrobial, antifungal, antioxidant, antidiarrheal, and wound-healing effects. Specifically, bark extracts have shown notable anti-inflammatory effects in rodent paw edema models and in preclinical models of pulmonary emphysema. A. colubrina seed-derived alkaloids are well-documented for their potent psychoactive properties, traditionally employed in ceremonial contexts. However, despite their ethnopharmacological relevance, these compounds can exert significant toxicological effects, with potential cardiotoxic and neurotoxic effects. Conversely, the gum exuded by the plant is composed of high-arabinose heteropolysaccharides, which have been reported to possess significant wound-healing and antidiarrheal potential, while presenting low toxicity and good safety characteristics. This review offers a critical synthesis of the current scientific literature on A. colubrina var. cebil, addressing its ethnobotanical relevance, biogeographical distribution, phytochemical profile, pharmacological activities, and toxicological properties. It is focused on the species' bioactive potential and identifies current knowledge gaps to guide future research.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Combinations of Natural and Synthetic Agents: A Novel Therapeutic Frontier in Breast Cancer Management.","authors":"Sadaf Arfi, Nimisha Srivastava, Vivek Bakshi, Nisha Sharma","doi":"10.2174/0113895575431891260131203159","DOIUrl":"https://doi.org/10.2174/0113895575431891260131203159","url":null,"abstract":"<p><p>Breast cancer is the most commonly and frequently occurring cancer in females in most of the developed and developing countries and is the main cause of cancer deaths in women (around 30% of newly diagnosed patients every year). Presently, various highly specialized and modern treatment and therapeutic methods for breast cancer are available such as radiotherapy, surgical method, hormonal therapy, immune therapy and chemotherapeutic drug treatment. Conventional cancer therapies have proposed various challenges, like toxicity, non-specific drug distribution, multidrug resistance and high cost of treatment. Natural bioactive molecules or phytochemicals are generally referred to as the compounds having specific biological activities in humans. Several Studies have shown that natural phytochemicals derived from certain plants have the capability to prevent carcinogenesis. The utilization of phytochemicals alone or combinational therapy of phytochemicals and synthetic drugs are providing excellent examples for chemoprevention against and therapy for human breast cancer. This comprehensive review revolves around the latest cancer treatment to treat breast cancer by utilising, phytochemicals such as Vinca alkaloids, piperine, resveratrol, curcumin, paclitaxel, silibinin, quercetin, genistein, and epigallocatechin Gallate etc. and combination of synthetic and phytochemical drugs to pave way to combination therapy.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-Derived Fucoidan in Cancer Therapy: Mechanistic Insights, Clinical Prospects, and Future Directions.","authors":"Yutian Qin, Wenqing Wang, Yiqiong Wang, Dai Kuang, Mamy Jayne Nelly Rajaofera","doi":"10.2174/0113895575425683260125222632","DOIUrl":"https://doi.org/10.2174/0113895575425683260125222632","url":null,"abstract":"<p><strong>Background: </strong>Cancer treatment faces persistent challenges of efficacy and toxicity with conventional therapies. Fucoidan, a sulfated polysaccharide derived from brown algae, demonstrates significant anticancer potential through multiple mechanisms, positioning it as a promising therapeutic candidate for improving cancer care outcomes.</p><p><strong>Objective: </strong>This review examines fucoidan's antitumor activities and evaluates its potential as a therapeutic agent in cancer treatment.</p><p><strong>Methods: </strong>Literature analysis encompassed peer-reviewed research on fucoidan's anticancer properties, bioavailability challenges, and delivery innovations. The search explored structure-activity relationships, preclinical evidence across cancer types, and early clinical trial results when combined with standard treatments.</p><p><strong>Results: </strong>Fucoidan exhibits multiple anticancer mechanisms including apoptosis induction, cell cycle arrest, angiogenesis inhibition, and immunomodulation. Preclinical studies demonstrate efficacy across various cancer types, with early clinical trials showing promise when combined with standard treatments.</p><p><strong>Conclusions: </strong>Fucoidan represents a promising marine-derived compound for precision oncology. Despite challenges in bioavailability and standardization, innovative approaches like nanoencapsulation show potential to overcome these limitations. Future research priorities include comprehensive structure-activity relationship studies, optimized delivery systems, and rigorous clinical trials to translate fucoidan's therapeutic benefits from bench to bedside.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naturally Occurring and Synthetic Coumarin Derivatives: Promising Agents for Managing Neuroinflammation.","authors":"Seyedeh Niloufar Ghafouri, Navid Dastyafteh, Aida Iraji, Mohammad Mahdavi, Mina Saeedi","doi":"10.2174/0113895575439030260122105248","DOIUrl":"https://doi.org/10.2174/0113895575439030260122105248","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Neuroinflammation is characterized by the activation of the brain's immune system, mainly involving microglia and astrocytes, in response to injury, infection, or neurodegenerative processes. It leads to neuronal damage, playing a key role in the onset and progression of neurological disorders. Lipopolysaccharide (LPS)-induced models have become pivotal in the study of neuroinflammation and its related complications. Coumarin derivatives-both natural and synthetic derivatives- have shown a promising effect on neuroinflammatory pathways.</p><p><strong>Methods: </strong>This review studied findings from published studies on naturally occurring and synthetic coumarin derivatives with anti-neuroinflammatory activity. Literature was surveyed by Google Scholar, Scopus, PubMed, and Web of Science without date restrictions. Specific emphasis was placed on compounds evaluated using BV2 microglial cells and LPS-induced inflammation models.</p><p><strong>Results: </strong>Coumarins demonstrated significant inhibitory effects on key inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytokines like TNF-α and IL-6. Natural compounds such as kellerin and ferulaferone B, and synthetic agents like compounds 28 and 38, exhibited potent activity, often surpassing reference drugs. Compounds like 7-methoxycoumarin and 4-methylesculetin, both commercially available, have shown strong efficacy in animal studies.</p><p><strong>Discussion: </strong>Coumarins exhibited multitarget mechanisms, making them promising candidates for managing neuroinflammation.</p><p><strong>Conclusions: </strong>Translation of coumarins to clinical use requires further research to ensure safety and effectiveness.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green-synthesized Titanium Dioxide Nanoparticles: Systematic Review of Antimicrobial Efficacy and Biocompatibility.","authors":"Gabriella R Silva, Bruna R A Leal, Ana B B A Ferro, Maria J B Silva, Weslley S Paiva, Danilo R Souza, Julio A Miranda, Everton N Alencar, Pedro H Sette-de-Souza, Moan J F Costa","doi":"10.2174/0113895575454226260126093115","DOIUrl":"https://doi.org/10.2174/0113895575454226260126093115","url":null,"abstract":"<p><strong>Background: </strong>Green-synthesized TiO2 nanoparticles represent sustainable alternatives to conventional antimicrobials combining strong bioactivity with lower environmental impact.</p><p><strong>Objective: </strong>This study evaluates their antimicrobial efficacy and cytotoxicity when produced via plant-mediated synthesis.</p><p><strong>Methods: </strong>A search was conducted in the PubMed, Web of Science, Scopus and EMBASE databases, following the PRISMA guidelines, with no restrictions on publication date or language. Eleven studies pub-lished between 2018 and 2025 were included by two independent reviewers, with methodological quality assessed using the QUIN tool for in vitro studies.</p><p><strong>Results: </strong>The nanoparticles exhibited predominantly spherical morphology and sizes ranging from 10 to 146nm, with pronounced broad-spectrum antimicrobial activity against Gram-positive bacteria (e.g., Staphy-lococcus aureus, Bacillus subtilis), Gram-negative bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa), and fungal species (e.g., Candida albicans, Aspergillus niger), with particularly remarkable potency against Gram-positive strains, displaying minimum inhibitory concentration (MIC) values as low as 0.125 µg/mL Mechanistic investigations implicated photocatalytically generated reactive oxygen species (ROS) as the principal driver of antimicrobial action, mediating oxidative stress, membrane destabilization, and cellular damage. Importantly, cytotoxicity assays demonstrated minimal deleterious effects on mammalian cells, with >80% viability maintained in HUVECs even at concentrations up to 1000 µg/mL highlighting the favorable biocompatibility of these nanomaterials.</p><p><strong>Conclusion: </strong>Nevertheless, heterogeneity in synthesis pro-tocols and the paucity of direct comparative studies with standard antibiotics underscore the necessity for methodologi-cal standardization. Collectively, these findings substantiate the potential of green-synthesized TiO₂ NPs as versatile can-didates for biomedical, agricultural, and environmental applications, while emphasizing the imperative for further opti-mization and translational validation.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Artificial Intelligence in the Medical Field for the Early Prediction, Diagnosis, and Detection of Various Comorbidities.","authors":"Namrata Singh, Rashmi Verma, Richa Saxena, Shalini Tiwari, Amit Juyal","doi":"10.2174/0113895575434558260202101416","DOIUrl":"https://doi.org/10.2174/0113895575434558260202101416","url":null,"abstract":"<p><p>The increasing comorbidity rates, which are described as a patient having more than two medical conditions, present a significant problem in contemporary healthcare. The co-occurrence of various disorders makes their diagnosis challenging, postpones clinical decision-making, and leads to unsatisfactory therapeutic gains in most cases. Traditional diagnostic and prognostic methods are often time-consuming, and they are lacking in the capability to precisely forecast the development of diseases and the interaction of comorbidities. These restraints provide the acute necessity of technological advancement of solutions that could improve the early diagnosis and clinical treatment. The review article focuses on the implementation of Artificial Intelligence (AI) in the initial prediction, diagnosis, and detection of different comorbidities. The use of these algorithms in medical diagnostics and the improvement of healthcare brought about a revolutionary shift in machine learning within the healthcare industry. Precise predictions on patient outcomes are now within reach, thanks to the training of algorithms on large medical datasets. With the help of AI-feeding systems, it is possible to integrate electronic health records, laboratory results, and medical imaging data to reveal specific correlations and initial risk factors that cannot always be observed by conventional methods. By keeping an eye out for small changes that could suggest health problems, machine learning helps doctors make accurate diagnoses and personalize treatments. The most prevalent application of this technology is to use supervised learning to develop an efficient treatment intervention plan based on patient data.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Roles of Small-molecule Derivatives in Modulating Neurodegenerative Pathways: From Molecular Targets to Therapeutic Applications.","authors":"Kuldeep Singh, Pranshul Sethi, Divya Jain, Jeetendra Kumar Gupta, Omar Awad Alsaidan, Sami I Alzarea, Arun Kumar, Mohammad Tabish, Mukesh Chandra Sharma","doi":"10.2174/0113895575429412260112060311","DOIUrl":"https://doi.org/10.2174/0113895575429412260112060311","url":null,"abstract":"<p><p>Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease involve progressive neuronal dysfunction driven by mechanisms including protein aggregation, oxidative stress, mitochondrial impairment, and neuroinflammation. Current treatments are largely symptomatic, with limited disease-modifying options. Advances in medicinal chemistry have led to the development of small-molecule derivatives targeting specific pathological pathways, offering new therapeutic opportunities. This review summarizes recent progress in designing and optimizing such molecules to modulate amyloid-β metabolism, tau acetylation, α-synuclein aggregation, RNA-binding protein interactions, and NLRP3 inflammasome activation. Compounds acting on key signaling cascades, including PI3K/Akt, MAPK/ERK, Nrf2/ARE, and Wnt/β-catenin, are discussed, alongside drug repurposing strategies and preclinical-to-clinical translation. Special focus is given to microglial modulation, challenges in crossing the blood-brain barrier, and integration of precision medicine, metabolomics, and artificial intelligence into drug discovery. The review also highlights novel therapeutic concepts such as multi- target ligands, metal-chelation approaches, and modulation of neuroinflammatory pathways. Despite promising leads, significant challenges remain in optimizing pharmacokinetics, target selectivity, and delivery. Future directions include the identification of robust biomarkers, advanced imaging techniques, and computational tools to accelerate candidate validation. Collectively, smallmolecule therapeutics hold considerable promise in addressing unmet needs in neurodegenerative disease management, but their successful translation will require multidisciplinary approaches bridging molecular insights and clinical application.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products as Autophagy-related Protein Kinase Inhibitors: A Future Promising Anticancer from Nature.","authors":"Wadah Osman, Mohamed Mirghani, Mona S Mohamed, Khaled M Elamin, Asmaa E Sherif, Mohammed H Alqarni, Ahmed I Foudah, Ahmed Ashour, Tariq M Aljarba, Hagar M Mohamed, Gamal A Mohamed, Sabrin R M Ibrahim","doi":"10.2174/0113895575425609260102211508","DOIUrl":"https://doi.org/10.2174/0113895575425609260102211508","url":null,"abstract":"<p><strong>Introduction: </strong>Autophagy plays a vital role in maintaining cellular homeostasis, and its dysregulation is closely associated with cancer progression. Targeting autophagy-related protein kinases has emerged as a promising therapeutic approach.</p><p><strong>Methods: </strong>This review analyzes studies retrieved from the PubMed database to identify natural products with inhibitory activity against autophagy-related protein kinases.</p><p><strong>Results: </strong>Plant-derived secondary metabolites, including polyphenols, alkaloids, terpenoids, and flavonoids, were identified as modulators of key autophagy-related kinases such as mTOR, AMPK, ULK1, and Beclin-1. These compounds regulate autophagy by influencing signaling pathways that control autophagosomal formation and degradation, thereby affecting cancer cell survival. They originate from diverse plant parts (such as leaves, seeds, and rhizomes) and exhibit activity across various cancer types, including hepatic, breast, lung, colorectal, gastric, and brain malignancies.</p><p><strong>Discussion: </strong>Although these natural compounds showed significant anticancer potential, challenges such as poor bioavailability and limited pharmacokinetics persist. Advances in nano-formulations, structural modifications, and structure-activity relationship-guided optimization have improved their efficacy.</p><p><strong>Conclusion: </strong>Overall, natural products targeting autophagy-related kinases hold great promise as leads for novel anticancer agents, warranting further in vivo validation, pharmacological optimization, and synergistic studies as adjuncts.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin: Chemical Foundations and Emerging Therapeutic Potential.","authors":"Shivaputra A Patil, Holly C Hunsberger","doi":"10.2174/0113895575429775260119043318","DOIUrl":"10.2174/0113895575429775260119043318","url":null,"abstract":"<p><p>Psilocybin, chemically known as (4-phosphoryloxy-N, N-dimethyltryptamine, 4-PODMT), is derived from the psychoactive mushroom genus, Psilocybe. Of the four active metabolites, psilocin readily enters systemic circulation. The psychoactive effects of psilocin are thought to arise through partial agonist effects at the 5-HT2A receptor. Psychedelic drugs, including psilocybin, are having a renaissance, especially in mental health disorders, addiction, and cancer-related depression. The beneficial effects of psilocybin are expanding into brain injury and lifespan due to its ability to enhance neuroplasticity. However, the large-scale synthesis of psilocybin was the main challenge for the scientific community after the FDA's breakthrough therapy designation in 2018 for Treatment- Resistant Depression (TRD) and for Major Depressive Disorder (MDD) in 2019. Synthesizing psilocybin is challenging due to the complex reactions, a multi-step process that requires strict temperature control, hazardous reagents, and purification difficulties. The very first Hoffman's synthetic method was successfully modified by several medicinal chemistry research groups to obtain it on a kilogram scale to conduct important clinical trials. This mini review comprises a brief history, chemistry, and pharmacology, along with the therapeutic use in depression of this naturally occurring psychedelic.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}