Mini reviews in medicinal chemistry最新文献

{"title":"Minoxidil as a Prodrug: Review of Chemical, Pharmacological, and Technological Aspects in Alopecia Therapeutics.","authors":"Gustavo Terra de Oliveira, Ana Beatriz Kimie Baiocco Ikegaki, Isadora Luziana Izidoro de Souza, Sandra Barbosa Neder Agostini, Maria Betânia de Freitas Marques, Magali Benjamim de Araújo","doi":"10.2174/0113895575433118260115212307","DOIUrl":"https://doi.org/10.2174/0113895575433118260115212307","url":null,"abstract":"<p><p>Alopecia is a prevalent condition that affects both sexes, characterised by miniaturisation of hair follicles and changes in the dynamics of the hair cycle, such as androgenetic alopecia associated with various systemic factors, including the COVID-19 pandemic. Minoxidil (base), initially developed as an oral antihypertensive, is currently used in the treatment of alopecia, acting as a prodrug that requires hepatic sulphation to generate its active metabolite, minoxidil sulphate. Topical formulations use minoxidil sulphate, the active pharmaceutical ingredient, directly on the hair follicles. Pharmacogenomic studies highlight the critical role of SULT1A1 enzyme variability in modulating treatment response, supporting personalised therapeutic strategies. Despite challenges related to low water solubility, high permeability, and narrow therapeutic index, emerging pharmaceutical technologies, including minitablets, orodispersible forms, sublingual preparations, and modified release systems, offer the potential to optimise absorption, increase dosing accuracy, and reduce adverse effects. This review consolidates current knowledge on the chemistry, pharmacology, pharmacogenomics, and technological aspects of minoxidil (base) for systemic use, emphasising translational developments that may redefine its clinical applications and contribute to safer and more standardised therapies. The integration of medicinal chemistry, pharmaceutical technology, clinical pharmacology, and regulatory guidance is expected to promote oral minoxidil as a reliable, effective, and patient-centred therapeutic option for alopecia.</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":"147513388","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":"Exploration of Schiff Bases: Structures, Syntheses, and Biological Activities.","authors":"Badr Sellami, Imane Yamari, Samir Chtita","doi":"10.2174/0113895575420281260116222032","DOIUrl":"https://doi.org/10.2174/0113895575420281260116222032","url":null,"abstract":"<p><p>Schiff bases are organic compounds that were first discovered in 1864 by German chemist Hugo Schiff. These bases result from a condensation reaction between a primary amine and a carbonyl compound, usually an aldehyde or a ketone. This reaction eliminates a water molecule and forms an imine group (-C=N-), the characteristic feature of Schiff bases. These bases are widely studied for their simple synthesis, structural diversity, and numerous applications in pharmacology. This review discusses their general structures and methods of synthesis. Schiff bases can be classified according to their structure (aliphatic or aromatic), denticity, and symmetry. Schiff bases have the ability to coordinate with metal ions such as copper (Cu2+), zinc (Zn2+), cobalt (Co2+), or nickel (Ni2+), allowing the formation of stable metal complexes, which enhances their biological properties. At the biological level, Schiff bases exhibit a wide range of activities due to their imine group. These include antibacterial, antifungal, antiviral, antitubercular, anti-inflammatory, antioxidant, anticancer, and other activities. This biological activity can be enhanced when Schiff bases complex with transition metals. In silico approaches play a crucial role in evaluating the therapeutic potential of Schiff bases and their complexes. These methods help predict their pharmacokinetic properties and binding affinity, thereby facilitating the rational design of more potent and selective therapeutic agents.</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":"147513396","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":"Iridoids as Multi-Target Neuroprotective Agents for Ischemic Stroke: Mechanisms and Therapeutic Potential.","authors":"Haiyi Gao, Mingtao Wang, Xinyue Zheng, Yian Zhao, Wenwen Li, Gongda Li, Hua Han, Peiliang Dong","doi":"10.2174/0113895575434105260102065611","DOIUrl":"https://doi.org/10.2174/0113895575434105260102065611","url":null,"abstract":"<p><p>Ischemic stroke continues to be a predominant global cause of death and long-term disability, with therapeutic options remaining notably constrained. Against this challenging backdrop, iridoids-natural monoterpenoids abundantly present in various medicinal plants-have gained significant attention as prospective neuroprotective agents for ischemic stroke. This comprehensive review systematically consolidates preclinical evidence regarding the therapeutic potential of ten representative iridoids, namely catalpol, picroside II, oleuropein, morroniside, loganin, aucubin, geniposide, cornin, gentiopicroside, and swertiamarin, utilizing data from diverse experimental stroke models. Accumulated findings reveal that these iridoid compounds mediate multi-modal neuroprotective benefits primarily through the regulation of crucial pathological cascades, such as excitotoxicity, persistent neuroinflammation, oxidative stress, apoptotic pathways, and blood-brain barrier integrity disruption. From a mechanistic standpoint, iridoids exert their influences by modulating a spectrum of vital signaling pathways, including VEGF/PI3K/Akt, Nrf2/HO-1, NF-κB, MAPK, and Bcl-2. These modulatory activities contribute to enhanced angiogenesis and neurogenesis, facilitate microglial polarization toward the protective M2 phenotype, and effectively mitigate oxidative damage and neuronal apoptosis. Given their pleiotropic mechanisms of action, iridoids constitute a highly promising class of natural scaffolds for developing innovative multi-target therapeutics for ischemic stroke. To advance their translational potential, subsequent research should emphasize structural optimization and synthetic derivatization to improve potency and pharmacokinetics. Concurrently, exploring advanced targeted drug delivery platforms appears imperative to maximize their bioavailability and brain penetration, thereby facilitating the transition of iridoid-based candidates from preclinical research to clinical application.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513453","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":"Antidiabetic Activity of Sulfonamide Derivatives.","authors":"Ahmed Amleh, M İhsan Han","doi":"10.2174/0113895575436530260108071913","DOIUrl":"https://doi.org/10.2174/0113895575436530260108071913","url":null,"abstract":"<p><p>Sulfonamide-based compounds have garnered significant interest in antidiabetic drug research due to their flexible structures and diverse range of biological effects. This review compiles studies on sulfonamide derivatives evaluated against key targets in type 2 diabetes, including α-glucosidase, α-amylase, DPP-4, and aldose reductase. Research indicates that changes, such as the use of transition metals, the inclusion of halogens, or the mixing of different chemical structures, can significantly affect their activity. Research on the Structure-Activity Relationship (SAR) reveals how the lipophilic, size-related, and electronic properties of these compounds influence their efficacy and selectivity. These substances can enhance insulin responsiveness, lower blood sugar levels, and mitigate problems associated with diabetes, according to animal research and laboratory tests on enzymes. Molecular docking, molecular dynamics, and ADMET predictions are examples of computer-based techniques that help clarify how these molecules interact with their targets and determine whether they are suitable as medications. Overall, the evidence suggests that sulfonamide derivatives can do more than affect carbohydrate-digesting enzymes- they also have antioxidant, anti-inflammatory, and insulin-sensitizing effects. Since they work in several ways, they are strong candidates for new oral treatments for type 2 diabetes. This review emphasizes the importance of integrating chemistry, biological testing, and computer modeling to expedite the development of sulfonamide-based antidiabetic drugs.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513378","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":"Development of Triazole based Anticonvulsants through Various Catalytic Approaches.","authors":"Shobha Rani, Shiva Teotia, Sumitra Nain","doi":"10.2174/0113895575410016251214175524","DOIUrl":"https://doi.org/10.2174/0113895575410016251214175524","url":null,"abstract":"<p><p>Triazole-containing compounds will result in the production of various pharmacologically effective drugs. Epilepsy is a severe neurological disorder primarily managed by controlling seizures using antiepileptic drugs, which are often related with side effects in rare circumstances and can be life-threatening. Triazolam and Alprazolam are both drugs containing a triazole ring, and these are well-established drugs that are used in the treatment of epilepsy. In the five-membered azole ring, triazole ring containing compounds consist of two carbon and three nitrogen atoms. Triazole, a heterocyclic compound, which contains at least two distinct elements in the ring that includes three nitrogen atoms and two carbon atoms as a part of the five-membered azole chain. The nitrogenous heterocyclic moiety triazole, which is commonly called pyrrodiazole, has the chemical formula C2H3N3. The triazole-containing derivatives with two different isomers are 1, 2, 3-triazoles and 1, 2, 4-triazoles. Triazole-containing compounds can be synthesized by various methods such as substitution reactions, ring opening, and rearrangement. Among these isomers of triazole, drugs containing 1,2,4-triazole possess different pharmacological properties such as antifungal, antineoplastic, antibacterial, antimycobacterial, and antiepileptic properties. 1,3,4-thiadiazole-linked 1,2,4-triazoles and 1,2,4-triazole-3-thione derivatives are important targets for potent anticonvulsant drug candidates in both clinical and preclinical studies. Many synthetic compounds have a structural characteristic of a 1, 2, 4-triazole ring with diverse therapeutic efficacy. 1,2,4-triazoles are a key scaffold in a large number of triazole derivatives that produce diverse pharmacological effects. This review focuses on the pharmacological significance and the synthesis of triazole derivatives in medicinal chemistry.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494067","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":"Quinone Derivatives as Nrf2 Activators: Antioxidant Effects, Therapeutic Potential, and Toxicity.","authors":"Melford Chuka Egbujor, David Chinemerem Nwobodo, Oluebube Ezenwafor","doi":"10.2174/0113895575436825260115100522","DOIUrl":"https://doi.org/10.2174/0113895575436825260115100522","url":null,"abstract":"<p><p>Quinone derivatives are redox-modulating scaffolds with notable antioxidant properties. Quinones are naturally occurring and synthetic conjugated cyclic diketones. Owing to their structural and chemical diversity, quinones possess diverse biological and pharmacological properties, including redox signaling, oxidative stress reduction, and modulation of redox cycling. They activate the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, a transcription factor responsible for cellular antioxidant defenses via their electrophilic interactions with cysteine residues in Kelch-like ECH-associated protein 1 (KEAP1) and consequent nuclear translocation of NRF2. They also scavenge free radicals. The ability to scavenge free radicals and modulate the NRF2 signaling pathway makes quinone derivatives therapeutic molecules in oxidative stress-mediated diseases. However, excessive exposure to quinones has been linked to toxicity and pro-oxidant consequences. Therefore, regulating quinone concentration is required to address toxicological issues. Despite their structural and functional diversity, structural adjustments for some quinones based on structure-activity relationship (SAR) analysis will be necessary to enhance their toxicological profile and therapeutic effects. Additionally, strategies such as controlled dosing and targeted delivery systems can be employed to address toxicological concerns and enhance the therapeutic potential of quinone derivatives. The current review provides comprehensive information on the NRF2-inducing activity, radical scavenging activity, therapeutic potential, and toxicological profile of quinone derivatives as redox-modulating agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494189","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":"Research Progress on Pyrazine-based Medicinally Active Compounds: A Review.","authors":"Karan Joshi, Omkumar Prajapati, Sadaf Mirza, Ponam Jamwal, Miloni Brambhat, Denish Prajapati, Rasana Yadav, Mahesh A Barmade, M R Yadav, Prashant Murumkar","doi":"10.2174/0113895575421765251128091319","DOIUrl":"https://doi.org/10.2174/0113895575421765251128091319","url":null,"abstract":"<p><p>Medicinal chemists are highly interested in pyrazine-based compounds due to their diverse biological roles and potential therapeutic applications for various disorders. This research examines the expansion of pyrazine-derived compounds between the years 2014 and 2025. This review emphasizes their established efficacy against Cancer, Tuberculosis, Alzheimer's disease, microbial infections, inflammation, and viral pathogens. Pyrazines have shown significant prospects for drug discovery caused by their ability to target several biological processes. This paves the way for novel therapies. We have discussed significant discoveries of pyrazines, their complex mechanisms, and the necessary future actions to enhance the utility of pyrazine-based compounds as pharmaceuticals.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494154","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":"Diamonds for the Mind: Exploring the Potential of Adamantane against Alzheimer's Disease.","authors":"Preeya Negi, Nitin Dnyaneshwar Arote, Vandana Bharat Patravale","doi":"10.2174/0113895575426460260130103605","DOIUrl":"https://doi.org/10.2174/0113895575426460260130103605","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the predominant type of dementia, emerging as a major health issue globally due to its increasing incidence and the limited approved therapies that provide only symptomatic relief. Adamantane, a diamondoid hydrocarbon with a distinctive cage-like structure, has emerged as a promising scaffold in medicinal chemistry due to its high lipophilicity, leading to good central nervous system bioavailability. Notably, memantine, an NMDA (N-methyl-daspartate) receptor antagonist, is an adamantane derivative that is approved by the U.S. Food and Drug Administration (US FDA) to manage moderate-to-severe AD symptoms. This review analyses the structure-activity relationship (SAR) of several adamantane derivatives and their relevance to AD. Amino-substituted adamantanes, such as amantadine and memantine, display anti-Alzheimer potential due to improved NMDA receptor affinity and CNS permeability. Additional targets, such as voltage-gated sodium channels and retinoid receptors, are proposed as potential targets for adamantane derivatives developed to act against AD. While various adamantane compounds have been patented and studied, few have become clinically approved drugs. Structural changes, particularly at bridgehead carbon atoms, greatly influence pharmaceutical results. Adamantane's physicochemical features make it a preferred framework for future CNS-targeted therapies. Given the increasing need for more effective AD treatments, adamantane-based compounds present a viable option for new drug development.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494117","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":"Exploring the Therapeutic Potential of Sulfonamide-1,3,4-Thiadiazole Hybrids: Focus on Neurological and Infectious Diseases.","authors":"Bharti Bansal, Monika Gupta","doi":"10.2174/0113895575427760260120203139","DOIUrl":"https://doi.org/10.2174/0113895575427760260120203139","url":null,"abstract":"<p><p>The 1,3,4-thiadaizole is widely recognized in drug discovery for its favorable physicochemical characteristics and diverse range of biological activities. This heterocyclic compound contains a five-membered ring composed of nitrogen, carbon, sulfur, and oxygen atoms. The presence of sulfur in the thiadiazole ring enhances lipophilicity and membrane permeability, making these compounds attractive for medicinal development. Sulfonamides, which consist of a sulfonyl group (-SO2) attached to a benzene ring, exhibit numerous pharmacological activities, including antimicrobial and anti-infective effects. This review aims to provide a comprehensive examination of hybrid derivatives combining 1,3,4-thiadaizole and sulfonamide moieties, highlighting their potential for enhanced biological efficacy against a broad spectrum of diseases. When these structural moieties are linked, the resultant compounds often display increased potency, improved selectivity, and superior drug-like properties compared with either scaffold alone. Recent advances in the design of such hybrids were summarized, their synthesis and characterization were discussed, and in-vitro and in-vivo findings on their biological activities were presented, along with Structure-Activity Relationship (SAR) studies. The objective of this review is to emphasize the benefits and opportunities of these hybrids and thereby encourage further research and development of novel therapeutic agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494163","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":"A Comprehensive Review on Homology Modelling in Drug Development: Methodologies, Tools, and Evaluation.","authors":"Priyanshu Nema, Arpana Purohit, Vandana Soni, Sushil Kumar Kashaw","doi":"10.2174/0113895575388386251212074901","DOIUrl":"https://doi.org/10.2174/0113895575388386251212074901","url":null,"abstract":"<p><p>The large accumulation of genomic and proteomic data has clearly established the need for accurate prediction of protein structure, especially with a view to enabling structurebased drug design. There are numerous ways to do this on computers these days, but one that distinctly stands out is homology modeling since it is fast, cheap, and consistent. It forecasts three-dimensional protein structures with unrecognized geometries by examining how they have evolved to date. This article provides an in-depth and up-to-date review of homology modeling. It addresses important steps, like discovering templates, sequence alignment, model building, loop refinement, side chain modeling, and structure validation. We have examined in detail the widely used tools, such as BLAST, MODELLER, Swiss-Model, SCWRL, PROCHECK, ProSA, and VERIFY3D. Also, it has been covered how artificial intelligence and machine learning can enhance these processes to be more precise, where little homology exists. Currently, a lot of focus is being placed on loop modeling problems, choosing a template, and structural validation procedures, like root mean square deviation (RMSD), Z-score, and Ramachandran plot statistics. In addition, we have examined how homology modeling is used in ligand docking and in lead optimization at the system level. The review offers great advice on how to speed up the drug-development process, especially for proteins that prove hard to crystallize or solve by X-ray crystallography. It does so by integrating concepts from bioinformatics, computational genomics, and structural biology into its design. We herein bridge traditional techniques and current computer technology to offer drug scientists a useful tool.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494120","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}