Future medicinal chemistry最新文献

{"title":"Design, synthesis and biological evaluation of a 4,6-di(aziridin-1-yl)-1,3,5-triazine-benzimidazole hybrid as a potential dual-targeting anticancer agent.","authors":"Ivan S Chernov, Alexandra V Protas, Elena А Popova, Olga S Shemchuk, Natalia V Petukhova, Gulalek Babayeva, Valeria M Tretiakova, Vyacheslav E Bulakov, Pavel K Kozhukhov, Olga V Mikolaichuk, Il'ya V Kornyakov, Vadim S Pokrovsky, Konstantin N Semenov, Vladimir V Sharoyko","doi":"10.1080/17568919.2026.2658014","DOIUrl":"10.1080/17568919.2026.2658014","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to develop a novel aziridine-1,3,5-triazine derivative combining DNA-alkylating aziridine rings with a benzimidazole-containing fragment associated with PARP-related chemotypes.</p><p><strong>Materials and methods: </strong>The synthesis of target (4,6-di(aziridin-1-yl)-<i>N</i>-(2-(4-((2-methyl-1<i>H</i>-benzo[<i>d</i>]imidazol-1-yl)methyl)-1<i>H</i>-1,2,3-triazol-1-yl)ethyl)-1,3,5-triazin-2-amine (<b>7</b>) was achieved through a multi-step approach, involving the synthesis of 2-methyl-1-(prop-2-yn-1-yl)-1<i>H</i>-benzo[d]imidazole (<b>3</b>) and subsequent click chemistry reaction with <i>N</i>-(2-azidoethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine (<b>6</b>). Protein modeling, docking and molecular dynamics were performed using the Schrödinger suite. Compound <b>7</b> was evaluated for cytotoxicity <i>in vitro</i> (HCT-116, U87, HeLa, A549 and ECV304 cell lines) by MTT assay, genotoxicity in HCT-116 cells by DNA-comet assay, and <i>in vivo</i> in A549 and HCT-116 xenografts in immunodeficient BALB/c Nude mice.</p><p><strong>Results: </strong>Docking/MD suggested a PARP-1 binding mode, with key interactions comparable to established inhibitors such as talazoparib and olaparib. <i>In vitro</i> cytotoxicity assays against HCT-116, U87, HeLa, and A549 cell lines revealed dose-dependent antiproliferative effects, with <i>IC</i>₅₀ values of 14.12, 33.52, 44.60, and 26.4 µM, respectively. <i>In vitro</i> genotoxicity assays showed that incubation of HCT-116 cell line with the compound <b>7</b> causes dose-dependent damage to DNA integrity. <i>In vivo</i>, compound <b>7</b> inhibited tumor growth in A549 xenografts (up to 75.1%, <i>p</i> < 0.05) and demonstrated dose-dependent activity in HCT-116 xenografts (up to 82.9% TGI at 6 mg/kg, i.v.).</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1195-1210"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of recent strategic advances in antiviral covalent inhibitors.","authors":"Bo Wang, Siyuan Wang, Jiwei Zhang, Meehyein Kim, Peng Zhan","doi":"10.1080/17568919.2026.2642579","DOIUrl":"10.1080/17568919.2026.2642579","url":null,"abstract":"<p><p>Targeted covalent inhibitors (TCIs) have emerged as a promising antiviral modality, functioning through irreversible or reversible modification of conserved nucleophilic residues within essential viral proteins. These agents are increasingly recognized in antiviral drug discovery due to their potential to achieve enhanced target engagement and prolonged pharmacological effects when appropriately designed, thereby addressing limitations of traditional inhibitors such as rapid resistance development and suboptimal efficacy arising from insufficient binding durability. This review summarizes strategic frameworks for antiviral covalent inhibitor development, highlighting seminal and field-defining reports as well as recent advances. It provides a systematic overview of progress in high-throughput screening, mechanistic studies, and the integration of computational chemistry with artificial intelligence, thereby offering insights into the rational design and discovery of next-generation covalent antivirals.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1085-1099"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin and derivatives: therapeutic potential in the patent landscape.","authors":"Silvia Vitoria Silva Cezar, Alcimary Bispo Santos, Naira Nice Dos Santos, Marcela Bernardes Brasileiro, Anamaria Mendonça Santos, José Adão Carvalho Nascimento Júnior, Didier Bereau, Mairim Russo Serafini","doi":"10.1080/17568919.2026.2658011","DOIUrl":"10.1080/17568919.2026.2658011","url":null,"abstract":"<p><p>Natural compounds represent approximately 35% of the pharmaceutical market, gaining prominence in the treatment of various diseases. Among them is chrysin, a flavonoid with notable antimicrobial and immunomodulatory activities. However, its low aqueous solubility and chemical instability limit its therapeutic use, highlighting the need for more soluble pharmaceutical carriers or derivatives, as well as patent analysis to map technologies and therapeutic development opportunities. Therefore, this study aimed to identify and explore trends in therapeutic strategies related to the action of chrysin and its derivatives in different pathologies, as well as their potential to increase clinical efficacy through pharmaceutical technologies. A technological survey was conducted on 36 patents registered between 1999 and 2025 in different databases. The analysis revealed peaks in patent applications in 2019 and 2024, with China as the main country and universities as the primary type of applicant. The patents demonstrated that chrysin and its derivatives exhibit complex immunological and pharmacological activities, acting on multiple cellular targets and signaling pathways. These include the inhibition of enzymes and proteins, modulation of inflammatory pathways, gene regulation, and other mechanisms. This pharmacological diversity of chrysin reinforces its relevance in patent applications, proving its efficacy and enabling new applications or therapeutic combinations.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1295-1316"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel pyrimidine-triazole conjugates for targeted inhibition of EGFR: synthesis and biological evaluation.","authors":"Subhadip Maity, Priya Devi, Aastha Singh, Anjali Saxena, Biswajit Saha, Abuzer Ali, Vivek Asati","doi":"10.1080/17568919.2026.2658435","DOIUrl":"10.1080/17568919.2026.2658435","url":null,"abstract":"<p><strong>Aim: </strong>To design, synthesize, and evaluate novel pyrimidine-triazole derivatives as epidermal growth factor receptor (EGFR) inhibitors for anticancer activity.</p><p><strong>Materials and methods: </strong>Ten derivatives (<b>SM-1A to SM-1J</b>) were synthesized and assessed for cytotoxicity against A549 lung cancer cell line also performed EGFR inhibition assay. Molecular docking was performed on the ATP binding pocket of EGFR (PDB: 1XKK).</p><p><strong>Results: </strong>Compounds <b>SM-1F</b> and <b>SM-1 G</b> exhibited good cytotoxic activity (IC₅₀ = 0.5 and 0.7 µM) than standard drug erlotinib (IC₅₀ = of 0.9 µM). Compound <b>SM-1F</b> showed a good binding score -8.93 kcal/mol and interactions with amino acid residues THR 854, THR 790, CYS 775, and PHE856.</p><p><strong>Conclusions: </strong>The results showed SM-1F may be used as a lead compound for further development of novel EGFR inhibitors.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1227-1237"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targets for bacterial resistance: recent advances in small-molecule FtsZ inhibitors.","authors":"Wu-Bin Shao, Xiang Zhou, Song Yang, Ying Zhou","doi":"10.1080/17568919.2026.2642580","DOIUrl":"10.1080/17568919.2026.2642580","url":null,"abstract":"<p><p>ESKAPE pathogens (including <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and <i>Enterobacteriaceae</i>) represent a core challenge in the global antimicrobial resistance (AMR) crisis. Their multidrug resistance and high transmissibility pose severe clinical threats. However, the pharmaceutical industry's current motivation for developing new drugs targeting these resistant bacteria remains insufficient. Consequently, creating antibiotics with novel mechanisms of action has become a strategic imperative for safeguarding global public health security. Therefore, targeting the bacterial cell division core protein filamentous heat-sensitive Z (FtsZ) has emerged as a key strategy to address the AMR crisis. FtsZ exhibits high conservation and prokaryotic specificity, making it an ideal target for developing novel antimicrobial agents. This paper systematically reviews the structural and functional mechanisms of FtsZ and summarizes research progress on inhibitors targeting its GTPase activity or assembly process - including natural products, synthetic small molecules, peptides, and nanomaterials - based on their sources and structural types. Consequently, drug development targeting FtsZ holds promise as a breakthrough solution for treating infections caused by drug-resistant bacteria such as ESKAPE pathogens.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1133-1152"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanosynthesis and computational studies of new imidazole-based selenium adducts as potential anticancer agents against human prostate and cervical cancer.","authors":"Ghazanfar Abbas, Tanveer Hussain Bokhari, Muhammad Adnan Iqbal, Saima Rehman, Akbar Ali","doi":"10.1080/17568919.2026.2648984","DOIUrl":"10.1080/17568919.2026.2648984","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to design and synthesize three new selenium adducts to evaluate their anticancer potential against human prostate cancer (PC3) and cervical cancer (HeLa) cell lines using MTT assays.</p><p><strong>Materials and methods: </strong>Imidazole-based selenium adducts, 1,3-dipropyl-1,3-dihydro-2H-imidazole-2-selenone (<b>C₁</b>), 1-butyl-3-propyl-1,3-dihydro-2H-imidazole-2-selenone (<b>C₂</b>), and 1,3-dihexyl-1,3-dihydro-2H-imidazole-2-selenone (<b>C₃</b>), were prepared by using their corresponding symmetric and unsymmetrical <i>N</i>-alkylated mononuclear imidazolium salts under solvent-free conditions through a mechanochemical approach instead of the conventional solution method. All synthesized compounds were characterized using elemental analysis, UV-visible, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques.</p><p><strong>Results and conclusions: </strong>The prepared compounds exhibited higher cytotoxicity against cancer cell lines than against normal cells. The results revealed that selenium adducts were more potent than their respective azolium salts. Among the test compounds, <b>C₃</b> showed significant anticancer potential against both PC3 and HeLa cell lines with reasonably good IC₅₀ values of 5.75 ± 0.21 µM and 7.86 ± 0.12 µM, respectively. Theoretical studies, comprising molecular docking and DFT analysis, reinforced the experimental results and suggest that selenium adducts can be used as new anticancer agents.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1059-1069"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wogonin-derived chemotype enables discovery of novel GLS1 inhibitors with potent antitumor activity.","authors":"Xuhong Li, Yan Liang, Xiaoyu Zhang, Yongsheng Wu, Tizhi Wu, Yucheng Tian, Cheng Tang, Zhixia Qiu, Hongxi Wu, Jinlei Bian, Zhiyu Li, Xi Xu, Jubo Wang","doi":"10.1080/17568919.2026.2642584","DOIUrl":"10.1080/17568919.2026.2642584","url":null,"abstract":"<p><strong>Aims: </strong>This study evaluates <b>LX-191</b>, a wogonin-derived glutaminase-1 (GLS1) inhibitor featuring a non-<b>BPTES</b> chemotype, designed to overcome the limitations of existing GLS1-targeted therapies.</p><p><strong>Materials and methods: </strong>Following targeted screening to identify the flavone-based inhibitor <b>LX-191</b>, we assessed its GLS1 inhibitory potency and antiproliferative effects in A549 and HCT116 cells. <i>In vivo</i> therapeutic efficacy was evaluated using an A549 xenograft model, alongside mechanistic studies to determine its impact on oncogenic signaling.</p><p><strong>Results: </strong><b>LX-191</b> effectively inhibited GLS1 (IC₅₀ = 15.17 μM) and demonstrated potent antiproliferative activity in A549 and HCT116 cells. In A549 xenografts, <b>LX-191</b> achieved 50.3% tumor growth inhibition at 10 mg/kg, outperforming <b>CB-839</b> (21.6%) under identical conditions. Mechanistically, <b>LX-191</b> attenuated glutamine metabolism while concurrently suppressing signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) signaling, leading to G1 phase cell cycle arrest and induction of autophagy.</p><p><strong>Conclusions: </strong>The findings establish <b>LX-191</b> as a promising flavone-based, non-<b>BPTES</b> lead for GLS1 inhibition, exhibiting multi-pathway antitumor activity both <i>in vitro</i> and <i>in vivo</i>. This work provides a tractable lead compound for the development of next-generation GLS1 therapeutics.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1011-1024"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel multitargeted Imidazo[1,2-<i>a</i>]pyridine-1,3,4-oxadiazole hybrids: design, synthesis and biological evaluation as anti-Alzheimer's agents.","authors":"Drashti Shah, Ashish Patel, Alkesh Patel","doi":"10.1080/17568919.2026.2649001","DOIUrl":"10.1080/17568919.2026.2649001","url":null,"abstract":"<p><strong>Aims: </strong>To design, synthesize, and evaluate novel imidazo[1,2-<i>a</i>]pyridine derivatives as dual acetylcholinesterase (AChE) and β-secretase (BACE1) inhibitors for potential Alzheimer's disease (AD) therapy.</p><p><strong>Materials and methods: </strong>A series of imidazo[1,2-<i>a</i>]pyridine derivatives (<b>DS1-DS15</b>) were synthesized via cyclization using various aryl and heteroaryl acids and characterized by MP, TLC, FTIR, MS, and ¹H/¹³C NMR spectroscopy. Molecular docking studies were performed against AChE (PDB ID: 4EY7) and BACE1 (PDB ID: 4ACU). Pharmacokinetic properties were predicted using pkCSM, and molecular dynamics simulations were conducted for the lead compound. <i>In vitro</i> inhibitory activities were determined by IC₅₀ values. <i>In vivo</i> anti-AD activity was evaluated in male Sprague Dawley rats using biochemical assays and histological analysis.</p><p><strong>Results: </strong>Compound <b>DS7</b> showed the highest binding affinity toward both targets with stable protein-ligand interactions. It exhibited potent AChE inhibition (IC₅₀ = 0.054 µM) and significant BACE1 inhibition (IC₅₀ = 5.67 µM). <i>In vivo</i> studies demonstrated significant reversal of AD-associated biochemical and histopathological alterations at high dose.</p><p><strong>Conclusion: </strong><b>DS7</b> emerged as a promising dual AChE/BACE1 inhibitor and a potential lead candidate for further optimization in AD drug development.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1071-1084"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of novel antibacterial hybrids combining quinoline and thiazole moieties.","authors":"Mostafa M A Aref, Sami A Al-Hussain, Alyaa S Abdel Halim, Hamed I Ali, Magdi E A Zaki, Mennatullah N Abdelhamed, Zeinab A Muhammad","doi":"10.1080/17568919.2026.2658010","DOIUrl":"10.1080/17568919.2026.2658010","url":null,"abstract":"<p><strong>Aim: </strong>The emergence of bacterial resistance underlines the urgent need for antibacterial agents with novel structures and mechanisms. We designed quinoline-thiazole hybrids by combining two privileged pharmacophores with established antibacterial properties..</p><p><strong>Methods: </strong>Fifteen novel derivatives were synthesized from quinoline-thiosemicarbazone precursors via reactions with phenacyl bromide and chloroacetic acid, followed by aldehyde condensation. Structures were confirmed by spectral analyses. Antibacterial activity was evaluated against MSSA, MRSA, and VRSA strains, and the most potent compounds were further assessed for antibiofilm activity, Cytotoxicity against WI38 fibroblasts (MTT assay), and potential inhibition of D-alanine-D-alanyl carrier protein ligase (SaDltA) via molecular docking.</p><p><strong>Results: </strong>Nine compounds demonstrated potent activity against MSSA (MIC: 0.59-2.2 µM) and MRSA (MIC: 1.08-9.08 µM), comparable to vancomycin (0.34 and 1.35 µM, respectively). Notably, several derivatives surpassed vancomycin in antibiofilm activity against both MSSA and MRSA. Cytotoxicity assessment revealed a favorable safety profile (IC₅₀: 410.13-3246.1 µM). Molecular docking demonstrated significant <i>Sa</i>DltA binding (ΔG: -13.29 to -7.75 kcal/mol), suggesting a plausible mechanism for MRSA inhibition.</p><p><strong>Conclusion: </strong>Quinoline-thiazole hybrids exhibited potent antibacterial and antibiofilm activities, with favorable drug-like properties, positioning them as promising candidates for the treatment of multidrug-resistant staphylococcal infections.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1175-1193"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of indole hybrids as anti-bacterial and anti-fungal agents: synthetic protocols and SAR studies.","authors":"Sri Mounika Bellapukonda, Muhammed Anas Kt, Shivam Mishra, Ramakrishna Kodi, Subhendu Ghosh, Laxma Naik Korra, Srinivas Nanduri, Venkata Madhavi Yaddanapudi","doi":"10.1080/17568919.2026.2642582","DOIUrl":"10.1080/17568919.2026.2642582","url":null,"abstract":"<p><p>Antimicrobial resistance, a consequence of the prevalent overuse and misuse of antibiotics, has become a serious global health concern. While extensive drug discovery efforts are constantly underway to combat this, the relentless emergence of resistant pathogens demands innovative strategies beyond traditional approaches to address this pervasive health crisis. Among promising strategies, such as drug repurposing and novel chemotype development, molecular hybridization, particularly involving the versatile indole heterocycle, stands out. Its inherent structural flexibility offers unique avenues for optimizing pharmacokinetics, boosting biological activity, and enabling potent bioisosteric modifications. This review consolidates and analyzes advances in indole-based derivatives reported between 2017 and 2025, specifically as antibacterial and antifungal agents. Beyond simply listing advances, we critically integrated chemical synthesis with structure-activity relationships (SAR) and their associated biological activity emerging from a broad spectrum of indole-based modifications. By rigorously detailing these insights, we specifically aim to guide and accelerate the rational design of novel indole-based molecules, providing a vital framework for developing the next generation of antimicrobials to overcome emerging resistance mechanisms.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1101-1131"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}