Future medicinal chemistry最新文献_第2页

Synthesis, in vitro and in-silico evaluation of amide derivatives as prospective antimicrobial and antileishmanial agents. 酰胺类衍生物的合成、体外和计算机评价作为抗菌和抗利什曼病药物。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-17 DOI: 10.1080/17568919.2025.2479419

Haroon Ur Rashid, Sher Wali Khan, Abdul Latif, Saira Nayab, Muhammad Naveed Umar, Fatima Sana, Abdul Bari Shah, Muhammad Zahoor, Riaz Ullah, Essam A Ali

{"title":"Synthesis, in vitro and in-silico evaluation of amide derivatives as prospective antimicrobial and antileishmanial agents.","authors":"Haroon Ur Rashid, Sher Wali Khan, Abdul Latif, Saira Nayab, Muhammad Naveed Umar, Fatima Sana, Abdul Bari Shah, Muhammad Zahoor, Riaz Ullah, Essam A Ali","doi":"10.1080/17568919.2025.2479419","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479419","url":null,"abstract":"This study focused on the synthesis, antimicrobial, and antileishmanial evaluation of seven amide derivatives (AL-1 to AL-7). The target compounds were synthesized from L-cysteine methyl ester and various substituted aromatic and aliphatic carboxylic acids. The final products were characterized using physical and spectro-analytical techniques (FT-IR, 1H NMR). The derivatives were evaluated for their antimicrobial activity at various concentrations. Experimental studies revealed that compounds AL-5 and AL-6 were the most potent against Staphylococcus aureus and Escherichia coli, exhibiting 18 mm and 21 mm inhibition zones, respectively, at a concentration of 2000 µg/mL. Additionally, AL-5 and AL-6 showed significant activity against Candida albicans, with 20 mm and 23 mm inhibition zones, respectively, at a concentration of 1000 µg/mL. The compounds also exhibited moderate to good activity against Leishmania tropica. Compounds AL-2, AL-4, AL-5, and AL-6 demonstrated good activity, with IC50 values of 0.68 ± 0.09, 0.68 ± 0.16, 0.66 ± 0.08, and 0.68 ± 0.12 µg/mL, respectively. Molecular docking, in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, and Density Functional Theory (DFT) studies were conducted on the most potent compounds (AL-5 and AL-6) to validate and support their experimental antimicrobial and antileishmanial potential.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-breast cancer potential of thieno-pyrimidine derivatives as VEGFR-2 inhibitors. 噻吩嘧啶衍生物作为VEGFR-2抑制剂的抗乳腺癌潜力。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-17 DOI: 10.1080/17568919.2025.2479422

Aisha A Alsfouk, Maged Mohammed Saleh Al Ward, Mustafa A Al-Qadhi, Souad A El-Metwally, Reda G Yousef, Eslam B Elkaeed, Dalal Z Husein, Fatma G Amin, Hazem Elkady, Ahmed M Metwaly, Ibrahim H Eissa

{"title":"Anti-breast cancer potential of thieno-pyrimidine derivatives as VEGFR-2 inhibitors.","authors":"Aisha A Alsfouk, Maged Mohammed Saleh Al Ward, Mustafa A Al-Qadhi, Souad A El-Metwally, Reda G Yousef, Eslam B Elkaeed, Dalal Z Husein, Fatma G Amin, Hazem Elkady, Ahmed M Metwaly, Ibrahim H Eissa","doi":"10.1080/17568919.2025.2479422","DOIUrl":"https://doi.org/10.1080/17568919.2025.2479422","url":null,"abstract":"Background: Thieno-pyrimidine derivatives have emerged as promising candidates for VEGFR-2 inhibition. This study aimed to design, synthesize, and evaluate novel thieno-pyrimidine derivatives for their anti-cancer potential.Methods: A series of thieno-pyrimidine compounds were synthesized and screened for in vitro cytotoxicity against MDA-231 and MCF-7 cell lines. The most active compound, 6b, was further analyzed for VEGFR-2 kinase inhibition, wound healing, apoptosis induction, and cell cycle arrest. Molecular docking, 200 ns molecular dynamics simulations, MM-GBSA, ProLIF PCAT, and FEL analyses were conducted to assess binding stability. DFT calculations evaluated electronic properties, while in silico ADMET profiling predicted pharmacokinetics and toxicity.Results: Compound 6b exhibited potent cytotoxicity with IC50 values of 5.91 µM (MDA-231) and 7.16 µM (MCF-7). It demonstrated VEGFR-2 inhibition is comparable to sorafenib (IC50: 53.63 ± 3.14 nM). Wound healing assays showed significant inhibition of MDA-231 migration. Flow cytometry confirmed apoptosis induction (57.20% early apoptosis) and G1 phase arrest. Gene expression analysis revealed upregulation of pro-apoptotic markers and downregulation of Bcl-2. Computational studies confirmed stable VEGFR-2 binding, and ADMET predictions indicated a favorable safety profile.Conclusion: Compound 6b exhibits strong VEGFR-2 inhibition, potent anti-cancer effects, and a favorable toxicity profile, highlighting its potential for further therapeutic development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leading prodrug strategies for targeted and specific release. 领先的靶向和特异性释放前药策略。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-14 DOI: 10.1080/17568919.2025.2479412

Rupa Bargakshatriya, Sumit Kumar Pramanik

引用次数: 0

Leading designs of peptide-based chemical probes for medical imaging- the dawn of precision diagnostics. 用于医学成像的基于多肽的化学探针的领先设计-精确诊断的曙光。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-12 DOI: 10.1080/17568919.2025.2479415

Giuseppe Floresta

引用次数: 0

Design and application of CCR8 antagonists. CCR8拮抗剂的设计与应用。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-10 DOI: 10.1080/17568919.2025.2476381

Tom Van Loy, Dominique Schols, Steven De Jonghe

引用次数: 0

Key developments in fluorinated heterocycles. 氟化杂环的关键进展。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-06 DOI: 10.1080/17568919.2025.2476385

Carla Rizzo, Antonio Palumbo Piccionello

引用次数: 0

Synthesis of novel quinoline-thiazolobenzimidazolone hybrids as anticancer agents through caspase-dependent apoptosis. 通过caspase依赖性细胞凋亡合成新型喹啉-噻唑苯并咪唑酮类化合物抗癌药物。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-26 DOI: 10.1080/17568919.2025.2470112

Houria Bouria, Hayette Alliouche, Mohamed Imed Chouiter, Ali Belfaitah, Teresa Pacheco, Viktor Gala, David Pereira, Artur M S Silva

{"title":"Synthesis of novel quinoline-thiazolobenzimidazolone hybrids as anticancer agents through caspase-dependent apoptosis.","authors":"Houria Bouria, Hayette Alliouche, Mohamed Imed Chouiter, Ali Belfaitah, Teresa Pacheco, Viktor Gala, David Pereira, Artur M S Silva","doi":"10.1080/17568919.2025.2470112","DOIUrl":"10.1080/17568919.2025.2470112","url":null,"abstract":"Aim: This work explores the synthesis of new bi-heterocyclic hybrid compounds based on quinoline ring and investigates their potential as anticancer agents.Materials & methods: The novel fused quinoline-thiazolo[3,2-a] benzimidazole-3(2 h)one hybrids were prepared by regioselective nucleophilic ring opening of the corresponding quinolinyl-oxiranes. In vitro cytotoxic activity was evaluated against human lung (A549) and gastric (AGS) cancer cell lines.Results: Global results showed that all tested compounds have promising inhibitory properties. Compounds 17 and 18 bearing two methoxy groups on the quinoline ring have exhibited remarkable and interesting activities. The investigation of the cell death process showed that these compounds activated a caspase-dependent apoptosis pathway. Results were further supported by molecular docking studies.Conclusion: Both compounds exhibited good drug-like characteristics, which make them promising drug candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"543-555"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500287","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

Synthesis and in vitro antitrypanosomatid activity of novel 5-nitroindole-rhodanine conjugates. 新型5-硝基吲哚-罗丹宁偶联物的合成及体外抗锥虫活性研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-24 DOI: 10.1080/17568919.2025.2470110

Emce Badenhorst, Janine Aucamp, Christina Kannigadu, Helena D Janse van Rensburg, Keisuke Suganuma, David D N'Da

{"title":"Synthesis and in vitro antitrypanosomatid activity of novel 5-nitroindole-rhodanine conjugates.","authors":"Emce Badenhorst, Janine Aucamp, Christina Kannigadu, Helena D Janse van Rensburg, Keisuke Suganuma, David D N'Da","doi":"10.1080/17568919.2025.2470110","DOIUrl":"10.1080/17568919.2025.2470110","url":null,"abstract":"Aim: Trypanosomatid diseases, leishmaniasis and trypanosomiasis are vector-borne parasitic diseases that can cause death and catastrophic economic losses for millions of people. The growing resistance of trypanosomatid parasites to current treatments highlights the urgent need for new therapeutic agents. This study explored 5-nitroindole-rhodanine conjugates to identify promising new compounds with the potential for future development as antitrypanosomatid treatments.Materials and methods: The conjugates were synthesized in a multi-step process and evaluated in vitro for antileishmanial activity against Leishmania (L.) donovani and L. major strains. Cytotoxicity was assessed on Vero and THP-1 cells. Due to the taxonomic relation to Trypanosoma spp. the compounds were also screened for in vitro activity against species that cause zoonotic trypanosomiasis.Results and conclusion: Several hits were found with leishmanicidal activity against both L. donovani and L. major strains. Of these, 3d was identified as a potential early lead that exhibited nanomolar cidal activity against L. major, and greater selectivity than the reference drug amphotericin B. However, the compounds did not have similar activity levels against Trypanosoma spp. Hence, these compounds should be further investigated for their mechanism of action and in vivo antileishmanial activity to determine their potential as a leishmaniasis treatment.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"557-573"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491486","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

A comprehensive review on the latest advances of dimeric anticancer prodrugs. 二聚体抗癌前药的最新进展综述。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.1080/17568919.2025.2463884

Zhila Imani, Ebrahim Saeedian Moghadam, Zahra Imani, Mohsen Amini, Fatemeh Atyabi, Rassoul Dinarvand

{"title":"A comprehensive review on the latest advances of dimeric anticancer prodrugs.","authors":"Zhila Imani, Ebrahim Saeedian Moghadam, Zahra Imani, Mohsen Amini, Fatemeh Atyabi, Rassoul Dinarvand","doi":"10.1080/17568919.2025.2463884","DOIUrl":"10.1080/17568919.2025.2463884","url":null,"abstract":"The advancement of targeted drug delivery systems has opened up a wide array of opportunities in cancer therapy, leading to the exploration of various strategies. Among these, the use of prodrugs stands out as a particularly promising approach in targeted cancer treatment, aimed at enhancing the selectivity and effectiveness of cytotoxic agents. In the last few years, there has been considerable progress in the area of dimeric-based prodrugs aimed at cancer therapy. The advantages presented by dimeric-based prodrugs have significantly improved the efficiency of delivering anticancer drugs, characterized by a high drug loading capacity, advantageous pharmacokinetics, and drug release that responds to tumor stimuli. With respect to the importance of drug dimerization in the field of prodrug development, herein we review the latest reports covering research in dimeric prodrugs. We have categorized the article according to the reported anticancer agents. We have also spent a great deal of attention on different types of used linkers and methods of the dissociation of dimeric prodrugs into free monomeric drugs. Readers will easily be able to compare between the reported research using the same drugs with different linkers or different dissociation methods as well as different cancer cell lines targeted in the studies.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"709-723"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457537","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

Optimizing selective estrogen receptor degraders for anticancer drug development. 优化抗癌药物开发中的选择性雌激素受体降解剂。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-26 DOI: 10.1080/17568919.2025.2467615

Neha Bhatia, Shashank Kumar, Lajya Devi Goyal, Suresh Thareja

引用次数: 0