Mini reviews in medicinal chemistry最新文献

{"title":"The 1,3,4-Thiadiazole Scaffold in Medicinal Chemistry: Structural Insights, Mechanistic Pathways, and Therapeutic Outlook.","authors":"Ayush Katiyar, Ajay Kumar, Shashi Kiran Misra, Sanjay Kumar, Ashish Tiwari, Shivam Kumar, Shweta Singh Verma, Amrita Singh","doi":"10.2174/0113895575481902260831112205","DOIUrl":"https://doi.org/10.2174/0113895575481902260831112205","url":null,"abstract":"<p><p>Heteroatoms are common structural fragments in many APIs and excipients. Several heterocyclic scaffolds are considered privileged structures. The term Thiadiazole comes from the \"Hantzsch-Widman\" nomenclature and falls within the category of azole chemicals. These are heterocyclic compounds with 5-membered rings that contain 2 nitrogen atoms and 1 sulfur atom. It exists in 4 isomeric forms, namely 1,2,4-thiadiazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, and 1,2,5- thiadiazole. The thiadiazole nucleus shows a broad spectrum of biological activities, including antimicrobial, anticonvulsant, anticancer, antiviral, antituberculosis, anti-inflammatory and analgesic, diuretic, antidiabetic, anti-ulcer, antimalarial, and anti-leishmanicidal properties, as well as effects against influenza, hypolipidemia, hyperlipidemia, and hypertension. The most studied of these scaffolds is the 1,3,4-thiadiazole scaffold, and the synthesis of 1,3,4-thiadiazole proceeds through wellestablished reaction pathways, including the intramolecular cyclization of thioacylated intermediates, including acylhydrazide or thiosemicarbazide derivatives, which are either acid- or basecatalyzed and often facilitated by harsh dehydrating agents. The review also addresses the chemical reactivity, substitution behaviour, and stability of the scaffold under various conditions, thereby making it more adaptable for molecular design. Aromatic stability, unique electron distribution, and bioisosteric physicochemical and electronic characteristics of the 1,3,4-thiadiazole core result in improved pharmacodynamic and pharmacokinetic performance, and the use of the 1,3,4-thiadiazole ring is currently and, in the future, a major structural motif in drug discovery. This review summarizes emerging information on the chemistry of 1,3,4-thiadiazole and promotes the exploration of this versatile scaffold for developing new therapeutic agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016888","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 Review of Functional Differences Among Foamed Micro-tablets, Conventional Effervescent Tablets, and Fast-melt Tablets.","authors":"Ke Dong, Brian Wood, Patrick Antolak","doi":"10.2174/0113895575485520260902105625","DOIUrl":"https://doi.org/10.2174/0113895575485520260902105625","url":null,"abstract":"<p><p>Foamed micro-tablets (FMTs) are small-sized effervescent tablets (ETs) that retain many functionalities typically associated with conventional ETs. However, FMTs are not merely miniature versions of ETs; they represent an innovative dosage form that delivers health benefits and offers numerous advantages that traditional ETs cannot provide. Fast-melt tablets (FTs), which may resemble FMTs, are also discussed in comparison with both ETs and FMTs. This review aims to explore the functional similarities and differences among FMTs, conventional ETs, and FTs, as well as the mechanisms underlying these variations. For example, FMTs have a higher active load and a quicker release of active ingredients than FTs due to their higher specific surface area (SSA). FMTs can also combine incompatible actives into a single dose, delivering synergistic health benefits from a mixture of different tablets. Multiple means of consumption are another key and distinct attribute of FMTs, as they can be consumed either by dissolving in water and drinking or by taking them directly to the mouth. In contrast, ETs can only be consumed after complete disintegration in water, whereas FTs are taken directly in the mouth. It is also noted that FTs disintegrate more quickly than FMTs and ETs, which are easier for people with swallowing difficulties. The mechanism for rapid disintegration of FTs is quite different: the dry tablet is placed in the mouth, where it disintegrates rapidly. This is primarily due to the use of superdisintegrants in the base FT formulation rather than the effervescent mix used in ETs and FMPs. This paper provides a detailed examination of the advantages and limitations of FMTs, ETs, and FTs, providing the first comprehensive review of these three dosage forms.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012614","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":"Macrophage Dynamics in Diabetic Wounds: Mechanisms, Signalling Pathways, and Therapeutic Innovations.","authors":"Nithya S, Jenanee Velayuthem, Anamika Padmavathy Krishnan, Anita Anand, Vedhapal Jeyamani, Akchaya B, Rithika S, Charulatha D, Porselvi Arumugam","doi":"10.2174/0113895575487146260831113744","DOIUrl":"https://doi.org/10.2174/0113895575487146260831113744","url":null,"abstract":"<p><p>Diabetic wounds are among the most challenging complications of diabetes mellitus, and approximately one in four patients with diabetes is expected to develop such a wound during their lifetime. The majority of diabetes-related amputations are attributable to complications of diabetic wounds. In conditions characterized by impaired wound healing, macrophage polarization is dysregulated, primarily due to the persistence of M1 macrophages and a delayed switch to the reparative M2 phenotype. This article reviews the molecular, signalling, and epigenetic mechanisms that regulate macrophage function in diabetic wound healing. The key signalling pathways PI3K/AKT, NF-κB, and Notch play essential roles in determining the balance between inflammatory and reparative processes, whereas DNA methyltransferases, histone-modifying enzymes, and non-coding RNAs control the transcriptional programs that drive macrophages toward either the M1 inflammatory or the M2 reparative phenotype. This review examines how emodin and Astragalus Polysaccharides (APS) modulate these mechanisms to promote M2 polarization and reduce oxidative stress in diabetic wounds. Immunomodulatory hydrogels, extracellular vesicles, and genetargeted nanoparticles can deliver this reprogramming potential directly to the wound site; however, clinical translation remains difficult because macrophage phenotype shifts unpredictably in the in vivo wound environment, and no current platform achieves reliable targeted delivery to wound macrophages. Future research should combine such delivery vehicles with epigenetic and gene-editing tools to restore immune equilibrium and tissue regeneration. Ultimately, modulation of macrophage plasticity may enhance diabetic wound healing and reduce the global burden of chronic non-healing ulcers.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012567","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 Molecules as Modulators of Drug Resistance: Emerging Strategies.","authors":"Manjot Singh, Saurabh Singh, Kalpana Rahate, Krishna Kamal","doi":"10.2174/0113895575496291260904053617","DOIUrl":"https://doi.org/10.2174/0113895575496291260904053617","url":null,"abstract":"<p><p>Cancer drug resistance remains a major challenge in oncology, limiting the long-term effectiveness of chemotherapy, targeted therapies, and immunotherapy. Resistance arises through multiple interconnected mechanisms, including overexpression of ATP-binding cassette (ABC) transporters, activation of pro-survival signaling pathways, persistence of cancer stem cells (CSCs), epigenetic alterations, and protective interactions within the tumor microenvironment (TME). These mechanisms collectively reduce drug accumulation, promote tumor survival, and contribute to disease recurrence and treatment failure. Natural molecules have emerged as promising modulators of drug resistance because of their ability to simultaneously target multiple resistance pathways. Polyphenols, flavonoids, alkaloids, terpenoids, saponins, and marine-derived compounds have demonstrated the capacity to inhibit ABC transporters, suppress CSC-associated signaling, regulate apoptotic pathways, and remodel the TME. Structure-activity relationship studies have identified key molecular features, including planarity, lipophilicity, and specific substitution patterns, that influence transporter inhibition and resistance- modulating activity. Furthermore, natural compounds have shown synergistic effects with conventional anticancer agents, enhancing chemosensitivity and therapeutic efficacy in preclinical models. Despite encouraging experimental evidence, clinical translation remains challenging due to poor bioavailability, pharmacokinetic variability, limited clinical validation, potential herb-drug interactions, and batch-to-batch inconsistencies in natural product preparations. Advances in nanotechnology- based delivery systems, artificial intelligence-assisted drug design, and biomarker-guided precision medicine are providing new opportunities to overcome these limitations. This review summarizes the major mechanisms of cancer drug resistance, highlights the role of natural molecules in resistance modulation, discusses current clinical evidence and translational challenges, and outlines future strategies for integrating natural product-based modulators into precision oncology.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012557","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":"Inflammatory Potential of Novel Phytochemicals: A Review of Current Evidence and Future Perspectives.","authors":"Ashutosh Mohanty, Gurudutta Pattnaik, Jyoshna Rani Dash","doi":"10.2174/0113895575448959260903181804","DOIUrl":"https://doi.org/10.2174/0113895575448959260903181804","url":null,"abstract":"<p><p>Inflammation is a multifaceted biological reaction to damaging stimuli that frequently results in diseases such as rheumatoid arthritis and neuropathic pain. Even though synthetic antiinflammatory medications are still often used, their side effects and growing resistance underscore the need for safer substitutes. Phytochemicals, which are bioactive substances derived from plants, present a promising therapeutic intervention option due to their low toxicity and diverse modes of action. The analgesic and anti-inflammatory properties of important phytochemical classes, including terpenoids, alkaloids, flavonoids, and phenolics, are highlighted in the discussion of their pharmacological significance. This review was conducted using a structured literature search to identify relevant studies on the anti-inflammatory and analgesic potential of phytochemicals. Electronic databases, including PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect, were systematically searched for articles published between January 2010 and June 2026. Earlier landmark studies were also included where necessary to provide historical context. The inclusion criteria comprised original research articles, review articles, systematic reviews, metaanalyses, and English-language clinical studies that investigated the anti-inflammatory or analgesic activities of phytochemicals, their molecular targets, signalling pathways, pharmacological mechanisms, or therapeutic applications. The exclusion criteria included non-English publications, conference abstracts without full text, editorials, letters, duplicate records, studies lacking adequate experimental evidence, and publications unrelated to phytochemical-mediated modulation of inflammation or pain. This work supports the development of plant-based substitutes for existing medications by integrating contemporary molecular insights with traditional ethnopharmacological expertise, highlighting the therapeutic potential of phytochemicals for treating pain and inflammation-associated illnesses.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012616","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":"Synthetic Strategies and Biological Activities of Pyrazolo[4,3-e]pyrrolo[1,2- a]pyrazines and Related Tricyclic Systems: A Comprehensive Literature Review.","authors":"Christian A Becerra R, Juan D Alarcón F, Paola A Cuervo P, L Orozco Fabian","doi":"10.2174/0113895575488539260827054553","DOIUrl":"https://doi.org/10.2174/0113895575488539260827054553","url":null,"abstract":"<p><p>Nitrogen-containing heterocyclic compounds with multiple fused rings have gained significant interest in medicinal chemistry due to their structural versatility and wide range of pharmacological applications. Within this category, pyrazolopyrrolopyrazines stand out as scaffolds featuring a tricyclic fused core composed of pyrazole, pyrrole, and pyrazine rings. These molecules have demonstrated promising biological activities, including potent antibacterial and antifungal properties, significant inhibition of phosphodiesterase type 5 (PDE5), and other activities. Moreover, analogous molecules have shown potential applications as antioxidants, anti-inflammatory agents, antitumor compounds, regulators of the vasopressin receptor AVPR1b, among others. Despite their potential, the development of unified and efficient synthetic methodologies for specific isomers- particularly less explored structural variants-remains limited and fragmented across the literature. This mini-review provides a comprehensive analysis of the synthetic strategies and biological potential of pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazine isomers and related tricyclic systems. This study discusses selected synthetic methodologies reported in the literature, ranging from classical synthetic methods to modern catalytic approaches, aiming to facilitate access to these heterocyclic analogs. Furthermore, this work identifies an existing research gap through the lack of systematic studies on the pyrazolo[3,4-e] isomer. To address this limitation, this study proposes a novel retrosynthetic strategy based on the stepwise construction of the tricyclic core from readily available 5- aminopyrazoles. This approach integrates well-established transformations, including nitrosations, reductions, Clauson-Kaas pyrrole formation, and Pictet-Spengler-type cyclization, for strategically construct this isomer of interest. This study presents precise and detailed breakdowns of each step, with the expressed priority of identifying common ground in analogous structures and reactivity between the literature and the proposal. By consolidating current knowledge, this review seeks to open new avenues for research on the design and functionalization of pyrazolopyrrolopyrazine derivatives, providing medicinal chemists with a valuable toolkit for developing new bioactive entities.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012579","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 New Dimension in Wound Care: Evaluating the Efficacy of Zinc Oxide Nanoparticle-based Therapies.","authors":"Lalit Kumar, Anju Goyal, Arijit Chaudhuri, Neelam Sharma, Biswajit Dash, Rajeev Arya, Ananya Balaji","doi":"10.2174/0113895575507577260827045549","DOIUrl":"https://doi.org/10.2174/0113895575507577260827045549","url":null,"abstract":"<p><strong>Introduction: </strong>Persistent infections, prolonged inflammation, and inadequate tissue regeneration often complicate delayed wound healing after mechanical trauma, diabetic ulcers, and burns. These challenges require new therapeutic strategies. Zinc oxide nanoparticles (ZnO-NPs) have been reported as promising candidates because of their pro-angiogenic, antibacterial, and antiinflammatory properties. This review aims to review the efficacy of ZnO-NP-based therapies in various wound types and formulation strategies.</p><p><strong>Methods: </strong>This literature review was performed in the fields of pharmaceutics, biotechnology, and regenerative medicine. We performed a comprehensive literature search on ScienceDirect, PubMed, and Google Scholar platforms, considering only peer-reviewed studies published from 2020 to 2026. The selected studies comprised in vitro and in vivo preclinical investigations of ZnO-NPbased wound treatments. In addition, granted patents were searched in Espacenet and Google Patents. Search keywords included \"zinc oxide nanoparticles,\" \"wound healing,\" \"diabetic ulcer,\" \"burn wound,\" \"hydrogel,\" \"nanofiber,\" and \"antibacterial\".</p><p><strong>Results: </strong>In preclinical models, ZnO-NP-containing dressings significantly accelerated wound closure by boosting collagen deposition, angiogenesis, and re-epithelialization while reducing inflammation. Advanced formulations, including stimuli-responsive hydrogels and hybrid systems, demonstrated better efficacy than conventional treatments (untreated wounds, vehicle-only dressings, and standard antibiotic ointments), often reaching closure rates above 90% in 14-21 days. Green synthesis improved the biocompatibility and antioxidant properties of ZnO-NPs.</p><p><strong>Discussion: </strong>Even though ZnO-NPs provide numerous advantages in wound management, they are still confronted with challenges such as dose-dependent cytotoxicity, batch variability in green synthesis, and inadequate clinical data. There is an increasing commercial interest in smart, multifunctional ZnO-NPs dressings, as evidenced by the patents of these technologies.</p><p><strong>Conclusion: </strong>Therapies that are based on ZnO nanoparticles introduce a novel aspect of wound care. With additional optimisation of safety, standardisation, and clinical translation, ZnO-NPs have the potential to significantly enhance the outcomes of acute and chronic wound treatment.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012554","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":"Oxadiazole-based Inhibitors Targeting Carbohydrate-Hydrolyzing Enzymes in Type 2 Diabetes Mellitus: Synthetic Strategies, Structure- Activity Relationships, and Translational Perspectives.","authors":"Shivank Sharma, Shubham Kumar, Pankaj Wadhwa","doi":"10.2174/0113895575480533260825083912","DOIUrl":"https://doi.org/10.2174/0113895575480533260825083912","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, progressive β-cell dysfunction, and chronic hyperglycemia, leading to microvascular and macrovascular complications. Among current therapeutic strategies, inhibition of intestinal carbohydrate-hydrolyzing enzymes, namely α-amylase and α-glucosidase, represents an established approach for controlling postprandial glucose excursions. However, clinically used inhibitors such as acarbose, miglitol, and voglibose are associated with gastrointestinal intolerance, limited selectivity, and variable efficacy, highlighting the need for improved therapeutic agents. In this context, 1,3,4-oxadiazole-based scaffolds have emerged as promising pharmacophores in antidiabetic drug design. The 1,3,4-oxadiazole ring acts as a bioisostere of amide and ester functionalities, conferring favorable physicochemical properties including enhanced metabolic stability, lipophilicity, and hydrogen-bonding capability. Structure-activity relationship (SAR) studies reported between 2015 and 2025 demonstrate that substituent effects-particularly phenolic hydroxyl groups, halogenation patterns, and extended aromatic systems-play a critical role in optimizing enzyme inhibition through hydrogen bonding, hydrophobic interactions, and π-π stacking within catalytic sites. While several oxadiazole-based hybrids incorporating privileged scaffolds such as benzimidazole, coumarin, and thiazolidinedione have been explored, evidence supporting modulation of additional targets including protein tyrosine phosphatase 1B (PTP1B), aldose reductase (ALR2), and inflammatory pathways such as the NLRP3 inflammasome remains limited and primarily derived from in vitro or computational studies. Computational approaches, including molecular docking, 3D-QSAR, and molecular dynamics simulations, have supported the rational optimization of oxadiazole derivatives, although their predictive limitations should be acknowledged. Despite encouraging preclinical findings, clinical translation remains constrained by insufficient pharmacokinetic, toxicological, and long-term efficacy data. Future research should prioritize systematic ADMET evaluation, standardized biological validation, and mechanistic expansion beyond carbohydrase inhibition to enable the development of clinically viable oxadiazole-based antidiabetic agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969916","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":"Computational and Natural Product Strategies in Anti-leishmanial Drug Discovery.","authors":"Debajyoti Roy, Pitam Ghosh, Maitrayee Ghosh, Niyati Acharya","doi":"10.2174/0113895575472560260825045017","DOIUrl":"https://doi.org/10.2174/0113895575472560260825045017","url":null,"abstract":"<p><p>Protozoan parasites from the genus Leishmania cause several neglected tropical diseases globally, which radically affect humans with a wide array of clinical manifestations ranging from cutaneous lesions to potentially fatal disease progression that may lead to death. Conventional methods of treating leishmaniasis using synthetic drugs are failing in major ways due to toxicity, high prices, the need for invasive routes of administration, and increasing reports of drug resistance against currently available medications. This review highlights the promising opportunity of combining two separate fields of natural product chemistry and computer-based drug discovery to develop new treatments for leishmaniasis. The present article provides a critical synthesis of data from both natural product bioactivity catalogues and methodology reviews to evaluate the translational feasibility of selected natural products with respect to their selectivity index and tiered classification for in vivo validation purposes; the identification of priority preclinical natural products based on the characterization of the most promising compound-target pairings will also be included in this article. This review also identifies numerous ongoing methodological limitations, including but not limited to: poor quality of external validation of quantitative structure-activity relationship (QSAR) modelling, activity data not being based on species-specific criteria, and difficulty linking structureactivity relationship (SAR) information with formulation types; and finally, this review provides evidence-based recommendations for enhancing the anti-leishmanial natural product development pipeline.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969985","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":"Lead Compound Discovery by Scaffold Hopping: Classification, Approaches and Application.","authors":"Harshada Rajendra Bafna, Nitin Rajendra Shirsath","doi":"10.2174/0113895575492610260817092827","DOIUrl":"https://doi.org/10.2174/0113895575492610260817092827","url":null,"abstract":"<p><strong>Introduction: </strong>In medicinal chemistry, scaffold hopping has become a crucial strategy for identifying new lead molecules with improved physicochemical, pharmacological, and intellectual property profiles. To underline its importance in modern drug discovery and lead optimization, this study was conducted.</p><p><strong>Methods: </strong>To gather data on scaffold-hopping techniques and their role in drug discovery, a thorough review of the published literature was conducted. Relevant scientific publications, reviews, and computational studies were methodically reviewed to categorize scaffold-hopping techniques, such as pharmacophore-based techniques, formalized scaffolds, ligand-based techniques, fragment and fingerprint-based techniques, scaffold abstraction, and biological similarity-based techniques.</p><p><strong>Results: </strong>The effectiveness of lead optimization, virtual screening, and scaffold identification has been significantly enhanced by the incorporation of artificial intelligence and machine learning. Successful applications have also been reported in the advancement of therapeutics for CNS disorders, diabetes mellitus, cancer, and inflammatory diseases.</p><p><strong>Discussion: </strong>The results highlight the critical role scaffold hopping plays in drug development by facilitating the creation of novel molecular frameworks with enhanced potency, pharmacokinetic characteristics, and patentability. Scaffold hopping continues to develop as a potent platform for increasing chemical diversity and meeting unmet medicinal needs, despite challenges related to synthetic feasibility, predictive accuracy, and experimental validation.</p><p><strong>Conclusion: </strong>The review illustrates its important contribution to contemporary medicinal chemistry by methodically describing its classifications, approaches, new computational techniques, and variety of therapeutic uses. From this study, we conclude that scaffold hopping is one of the most effective methods for discovering new drugs.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969990","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}