Future medicinal chemistry最新文献_第2页

Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents. 揭示了吡咯烷基小分子多功能抗糖尿病和抗癌药物的研究方向。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-12 DOI: 10.1080/17568919.2025.2501923

Shiv Kumar, Rupali Kohal, Debarshi Mondal, Shreya Kumari, Preety Kumari, Priya Bisht, Ghanshyam Das Gupta, Sant Kumar Verma

{"title":"Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents.","authors":"Shiv Kumar, Rupali Kohal, Debarshi Mondal, Shreya Kumari, Preety Kumari, Priya Bisht, Ghanshyam Das Gupta, Sant Kumar Verma","doi":"10.1080/17568919.2025.2501923","DOIUrl":"10.1080/17568919.2025.2501923","url":null,"abstract":"The pyrrolidine moiety, a five-membered saturated nitrogen-containing heterocycle, emerged as a crucial pharmacophore in medicinal chemistry due to its distinctive physicochemical properties, including hydrophilicity, basicity, and structural rigidity. Extensive modifications of pyrrolidine derivatives yielded novel compounds with pronounced antidiabetic and anticancer activities. The structural investigation of pyrrolidine-based molecules demonstrated that substitutions at the N1, 3rd, and 5th positions offer significant opportunities for optimizing biological activity and enhancing target-specific interactions. The synthesis of pyrrolidine-based molecules has been explored in literature; however, structural, target interaction analysis, and pharmacological aspects warranted for the development of targeted small molecule versatile antidiabetic and anticancer agents are lacking. The review addresses this gap by emphasizing the developments in pyrrolidine-based small molecules via structural and target interaction analysis, highlighting their antidiabetic and anticancer activities, and offering a comprehensive perspective on the development of targeted therapeutics. The investigated structural features and pharmacological developments underscore the dual functionality of pyrrolidine-based drugs in managing disorders, such as diabetes and cancer, that share common pathological mechanisms, such as inflammation, oxidative stress, and metabolic dysregulation. This overlap has catalyzed the development of multifunctional pyrrolidine derivatives capable of targeting pathways integral to both conditions, providing a promising avenue for therapeutic innovation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1039-1053"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987698","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}

引用次数: 0

Recent advances in quinazolinone derivatives: structure, design and therapeutic potential. 喹唑啉酮衍生物的最新进展：结构、设计和治疗潜力。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-11 DOI: 10.1080/17568919.2025.2504327

Feyzi Sinan Tokalı

引用次数: 0

Larvicidal potential of Knoevenagel adducts against Aedes aegypti: theoretical study and in vitro validation. Knoevenagel加合物对埃及伊蚊的杀幼虫潜力：理论研究和体外验证。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-05 DOI: 10.1080/17568919.2025.2498877

Paloma G Abrantes, Poliana G Abrantes, Renata R Magalhães, Gildilayne M Silva, Natália F Sousa, Marcus T Scotti, Renan T Leite, Jheison M C Francelino, Fabíola C Nunes, Juliana A Vale

{"title":"Larvicidal potential of Knoevenagel adducts against Aedes aegypti: theoretical study and in vitro validation.","authors":"Paloma G Abrantes, Poliana G Abrantes, Renata R Magalhães, Gildilayne M Silva, Natália F Sousa, Marcus T Scotti, Renan T Leite, Jheison M C Francelino, Fabíola C Nunes, Juliana A Vale","doi":"10.1080/17568919.2025.2498877","DOIUrl":"10.1080/17568919.2025.2498877","url":null,"abstract":"Aim: This study investigated the larvicidal potential of Knoevenagel adducts against Aedes aegypti larvae to develop sustainable alternatives for controlling disease vectors like dengue.Methods: Larvicidal activity of Knoevenagel adducts (1a-l) was evaluated on fourth-stage Aedes aegypti larvae. Additional analyses included nitric oxide measurement, cell profiling, toxicity assessment, molecular docking, molecular dynamics simulation, and ADMET (Absorption, Distribution, Metabolism, and Toxicity) evaluation.Results: Compounds 1c and 1g showed high larvicidal efficacy, with LC50 values of 3.39 and 5.13 ppm. Hemolymph analysis revealed altered hemocyte composition, indicating an immune response, though nitric oxide levels remained unchanged. Molecular docking identified strong interactions between the Aedes aegypti FKBP12 enzyme (PDB: 3UQI) and Knoevenagel adducts. Compound 1g had the highest activity probability and binding affinity, while 1c showed strong interactions validated by biological assays. Molecular dynamics confirmed stable interactions of 1c and FKBP12, with both 1c and 1g displaying significant van der Waals contributions. ADMET analysis highlighted 1c as a less toxic compound, with minimal mutagenic risk, favorable pharmacokinetics, and high bioavailability.Conclusions: Knoevenagel adducts 1c and 1g are promising candidates for effective, selective, and environmentally friendly larvicides.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"999-1011"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983567","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}

引用次数: 0

The antibreast cancer therapeutic potential of quinazoline hybrids-Part I. 喹唑啉杂合物的抗乳腺癌治疗潜力——第一部分。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-04-30 DOI: 10.1080/17568919.2025.2498881

Wei Chen, Ruo Wang, Yidan Lin, Xiaoqiang Wang, Feili Cai, Mengbo Lin, Jiawen Wang, Hui Zhang, Min Chen

{"title":"The antibreast cancer therapeutic potential of quinazoline hybrids-Part I.","authors":"Wei Chen, Ruo Wang, Yidan Lin, Xiaoqiang Wang, Feili Cai, Mengbo Lin, Jiawen Wang, Hui Zhang, Min Chen","doi":"10.1080/17568919.2025.2498881","DOIUrl":"10.1080/17568919.2025.2498881","url":null,"abstract":"Breast cancer is the most commonly diagnosed cancer in women and is the leading cause of cancer-related mortality among female patients across the world. Chemotherapy is a critical means for breast cancer therapy, and administration of chemotherapy could reduce the risk of recurrence by approximately one-third in early breast cancer. However, multidrug resistance represents a principal obstacle to effective chemotherapeutic interventions against breast cancer and is an increasing clinical challenge, creating an urgent demand to explore innovative chemotherapeutics to combat this formidable disease. Quinazoline hybrids with structural and mechanistic diversity exhibit excellent activity against breast cancers including drug-resistant forms and have the potential to reduce side effects caused by the corresponding pharmacophores. Notably, lapatinib, a quinazoline-furan-sulfone hybrid, has already been launched for breast cancer therapy. Thus, quinazoline hybrids represent a fertile source for the development of novel chemotherapeutics for clinical deployment in the control and eradication of breast cancer. This review emphasizes the current scenario of quinazoline hybrids with antibreast cancer therapeutic potential and focuses on structure-activity relationships (SARs) and modes of action, developed from 2020 onwards, to facilitate the rational discovery of more effective antibreast cancer candidates. [Figure: see text]This review emphasizes the current landscape of quinazoline hybrids with antibreast cancer therapeutic potential, delves into structure-activity relationships and mechanisms of action developed from 2020 onwards, aiming to facilitate the rational discovery of more effective and less toxic candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1055-1069"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011443","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}

引用次数: 0

In-silico and in-vitro evaluation of diazenyl compounds as anti-bacterial agents. 二氮基化合物作为抗菌药物的硅内和体外评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-15 DOI: 10.1080/17568919.2025.2504319

Shweta Tiwari, Gul Naz Fatima, Vimlesh Kumar, Shailendra K Saraf

{"title":"In-silico and in-vitro evaluation of diazenyl compounds as anti-bacterial agents.","authors":"Shweta Tiwari, Gul Naz Fatima, Vimlesh Kumar, Shailendra K Saraf","doi":"10.1080/17568919.2025.2504319","DOIUrl":"10.1080/17568919.2025.2504319","url":null,"abstract":"Aim: The diazenyls are interesting scaffold in medicinal chemistry displaying a wide range of pharmacological activities including anti-microbial, anti-cancer, anti-inflammatory, and analgesic-antipyretic, among others. These diverse attributes have reinitiated the interest of the researchers in them. Studies suggest that incorporating heterocyclic ring system into diazenyl scaffold helps to improve the biological property of the drug-like substances. The present study aims to synthesize novel diazinyl-triazole adducts, with an intent to obtain compounds with enhanced anti-bacterial potential.Materials and methods: All synthesized compounds were characterized using physicochemical methods and spectroscopic techniques. The compounds were evaluated in-vitro against two Gram-positive and two Gram-negative bacterial strains, demonstrating good to moderate efficacy. In-silico prediction study was also carried out for the synthesized series of compounds.Results and conclusion: The molecular docking data are aligned with the in-vitro experimental results. The ADMET predictions suggested the compounds are both efficacious and safe. The study presents new compounds as potential anti-bacterial agents with desirable pharmacological profile.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1013-1022"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077202","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}

引用次数: 0

Urea-sugar and thiourea-sugar diastereomers: synthesis, crystal structure and biological activities. 脲糖和硫脲糖非对映体：合成、晶体结构和生物活性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-14 DOI: 10.1080/17568919.2025.2504328

Özer Işilar, Adnan Bulut, Mustafa Tombul, Adem Güner, Onur Şahin

{"title":"Urea-sugar and thiourea-sugar diastereomers: synthesis, crystal structure and biological activities.","authors":"Özer Işilar, Adnan Bulut, Mustafa Tombul, Adem Güner, Onur Şahin","doi":"10.1080/17568919.2025.2504328","DOIUrl":"10.1080/17568919.2025.2504328","url":null,"abstract":"Aims: The principal objective of the conducted study is to synthesize enantiomerically pure a class of sugar-based (thio)ureas (9-12) and to investigate their antiproliferative activities against the A549 (lung cancer), MCF-7 (breast cancer), and PANC1 (human pancreatic cancer) cell lines.Materials and methods: The synthesis of (thio)urea sugars was performed by two stage procedure. First, the amino sugars (4 and 8) were obtained in three steps (tosylation, substitution and reduction). And secondly, the reaction of 3,5-bis(trifluoromethyl)phenyliso(thio)cyanate with the corresponding amines gave chiral (thio)urea derivatives (9-12). Cell viability was determined in human A549, MCF-7, PANC-1 and noncancer human embryonic kidney (HEK-293) cell lines.Results: Four chiral sugar (thio)ureas (9-12) were synthesized and screened against the A549, MCF-7, and PANC1 cell lines. Of the four chiral sugar derivatives, the compound 9 not only showed the best anticancer activity in the A549 cell line but also provided the highest normal cell (HEK-293) viability.Conclusion: From chiral sugar-derived (thio)ureas obtained, the compound 9 was found to be shown the highest activity against A549 cancer cell line. The compound 9, therefore, gave more promising results for future researches as anti-cancer agents. X-ray studies revealed that amide type hydrogens are playing important roles in anti-cancer activities.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"991-997"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077189","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}

引用次数: 0

Development of new anticancer thiadiazole-sulfonamides as dual EGFR/carbonic anhydrase inhibitors. 新型抗癌噻二唑-磺胺类EGFR/碳酸酐酶双重抑制剂的研制。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-08 DOI: 10.1080/17568919.2025.2498879

Ibrahim H Eissa, Hazem Elkady, Walid E Elgammal, Hazem A Mahdy, Hany S Elshennawy, Dalal Z Husein, Fatma G Amin, Ibrahim M Ibrahim, Bshra A Alsfouk, Eslam B Elkaeed, Ahmed M Metwaly

{"title":"Development of new anticancer thiadiazole-sulfonamides as dual EGFR/carbonic anhydrase inhibitors.","authors":"Ibrahim H Eissa, Hazem Elkady, Walid E Elgammal, Hazem A Mahdy, Hany S Elshennawy, Dalal Z Husein, Fatma G Amin, Ibrahim M Ibrahim, Bshra A Alsfouk, Eslam B Elkaeed, Ahmed M Metwaly","doi":"10.1080/17568919.2025.2498879","DOIUrl":"10.1080/17568919.2025.2498879","url":null,"abstract":"Background: Thiadiazole-sulfonamide derivatives were synthesized as dual inhibitors of epidermal growth factor receptor (EGFR) and carbonic anhydrase IX (CA-IX) to develop selective anticancer agents.Methods: Cytotoxicity was evaluated against MDA-MB-231 and MCF-7 breast cancer cells, with selectivity tested on Vero cells. Enzymatic inhibition studies were conducted against EGFR and CA-IX, using erlotinib and acetazolamide as reference drugs. Apoptosis was assessed through gene expression analysis of BAX/Bcl-2, caspase-8, and caspase-9, alongside flow cytometry for apoptosis and cell cycle analysis. Molecular docking and 200 ns molecular dynamics (MD) simulations evaluated binding interactions. Density Functional Theory (DFT) calculations and in silico ADMET predictions assessed stability, electronic properties, and safety.Results: Compound 14 exhibited potent cytotoxicity (IC₅₀ = 5.78 μM, MDA-MB-231; 8.05 μM, MCF-7) and high selectivity (IC₅₀ = 313.08 μM, Vero). It inhibited EGFR (IC₅₀ = 5.92 nM) and CA-IX (IC₅₀ = 63 nM), surpassing reference drugs. Apoptosis induction was confirmed by a 13.97-fold increase in BAX/Bcl-2, caspase upregulation, and G1-phase arrest. Computational analyses confirmed stable binding and favorable safety.Conclusions: Compound 14 represents a promising dual EGFR/CA-IX inhibitor with selective anticancer activity. Further in vivo studies are warranted.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1023-1038"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997919","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}

引用次数: 0

Targeting the complement system: notes on therapeutic strategies for renal cancer. 靶向补体系统：肾癌治疗策略综述。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-04-25 DOI: 10.1080/17568919.2025.2498876

Francesco Lasorsa, Monica Rutigliano, Martina Milella, Pasquale Ditonno, Giuseppe Lucarelli

引用次数: 0

Key advances and application prospects of PROTAC technologies in the next 5 years. 未来5年PROTAC技术的主要进展及应用前景。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-02 DOI: 10.1080/17568919.2025.2498875

Shuanglin Qin, Xiaohe Xiao

引用次数: 0

Evidence-based drug discovery. 循证药物发现。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-04-18 DOI: 10.1080/17568919.2025.2479762

Arash Sadri

引用次数: 0