Future medicinal chemistry最新文献_第5页

Latest developments of spirooxindoles and their derivatives in medicinal chemistry. 螺旋菌吲哚及其衍生物在药物化学中的最新进展。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-26 DOI: 10.1080/17568919.2026.2719228

Firoj Hassan, Nadimullah, Sabahat Yasmeen Sheikh, Iqbal Azad, Malik Nasibullah

{"title":"Latest developments of spirooxindoles and their derivatives in medicinal chemistry.","authors":"Firoj Hassan, Nadimullah, Sabahat Yasmeen Sheikh, Iqbal Azad, Malik Nasibullah","doi":"10.1080/17568919.2026.2719228","DOIUrl":"10.1080/17568919.2026.2719228","url":null,"abstract":"Spirooxindoles represent a pivotal class of heterocyclic compounds known for their diverse and potent biological activities. Naturally occurring spirooxindoles have been isolated from medicinal plants such as Flueggea virosa and Mitragyna speciosa, inspiring extensive research into their synthetic analogs. A variety of synthetic strategies, including multicomponent reactions, cycloaddition processes, and environmentally benign (green chemistry) approaches, have been developed to access structurally diverse spirooxindole derivatives. Recent investigations underscore their broad-spectrum bioactivity, including efficacy against drug-resistant bacterial and fungal pathogens, inhibition of the p53-MDM2 protein-protein interaction, and significant cytotoxicity against various human cancer cell lines. Advances in synthetic methodologies, notably microwave-assisted and catalyst-free protocols, have significantly improved the efficiency, selectivity, and sustainability of spirooxindole synthesis. This study summarizes recent developments in spirooxindole-containing compounds, both naturally isolated and synthetically prepared, reported in the last few years.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2575-2584"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817957","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

EGFR kinase inhibitors from novel thiazole derivatives: synthesis, anticolon cancer, docking, and ADME studies. 来自新型噻唑衍生物的EGFR激酶抑制剂：合成、抗结肠癌、对接和ADME研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 DOI: 10.1080/17568919.2026.2726191

Amani M R Alsaedi, Alaa M Abu Alnjaa, Amel S Younes, Zeinab A Muhammad, Sami A Al-Hussain, Magdi E A Zaki, Thoraya A Farghaly

{"title":"EGFR kinase inhibitors from novel thiazole derivatives: synthesis, anticolon cancer, docking, and ADME studies.","authors":"Amani M R Alsaedi, Alaa M Abu Alnjaa, Amel S Younes, Zeinab A Muhammad, Sami A Al-Hussain, Magdi E A Zaki, Thoraya A Farghaly","doi":"10.1080/17568919.2026.2726191","DOIUrl":"10.1080/17568919.2026.2726191","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is a key regulator of malignant cell growth and survival, making it an attractive target for cancer therapy. In this study, a new series of thiazole derivatives was rationally designed and synthesized as potential EGFR inhibitors and evaluated for their antiproliferative activity against two human colon cancer cell lines (HCT-116 and HT29). Several compounds exhibited potent anticancer activity, with compound 4j showing the highest potency, displaying half-maximal inhibitory concentration (IC50) values of 2.10 and 1.91 µM against HCT-116 and HT29 cells, respectively. Owing to its superior antiproliferative activity, compound 4j was further evaluated for EGFR inhibitory activity and demonstrated remarkable potency with an IC50 value of 0.27 µM. In addition, 4j exhibited a favorable selectivity index toward normal WI38 cells and effectively induced apoptosis through modulation of Bax, Bcl-2, and p53 expression. Molecular docking demonstrated strong binding interactions of 4j within the EGFR active site, while its ADME predictions supported its favorable drug-like profile. Overall, compound 4j represents a promising lead candidate for the development of novel EGFR-targeted anticancer agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2499-2509"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864343","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

Synthesis of novel thiazole derivatives linked benzonitrile moiety as potent antimicrobial agents. 新型噻唑类强效抗菌剂的合成。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-20 DOI: 10.1080/17568919.2026.2718759

Mariam A Al-Sheikh, Thoraya A Farghaly

{"title":"Synthesis of novel thiazole derivatives linked benzonitrile moiety as potent antimicrobial agents.","authors":"Mariam A Al-Sheikh, Thoraya A Farghaly","doi":"10.1080/17568919.2026.2718759","DOIUrl":"10.1080/17568919.2026.2718759","url":null,"abstract":"Aim: This study aims to design a new series of thiazoles by combining a thiazole core with a benzonitrile moiety via a suitable linker. Additionally, a hydrazone linker was employed to enhance molecular flexibility and facilitate favorable interactions within the DNA gyrase active site and testing their antimicrobial.Materials and methods: We synthesized a series of thiazole‑linked benzonitrile moiety through the reaction of thiosemicarbazone derivative with α-halocarbonyl reagents in basic refluxing dioxane. The novel derivatives were investigated for their antimicrobial activity.Results and conclusion: All derivatives showed excellent inhibition toward the used bacteria with inhibition zone diameter ranging from 10 to 35 mm. The evaluated thiazole derivatives exhibited superior antibacterial activity compared to antifungal activity, as none demonstrated efficacy against Aspergillus niger. Several derivatives showed antibacterial activity exceeded the reference drugs. Moreover, three derivatives 9, 13e, and 13h showed the same low values of both minimum inhibition concentration and minimum bactericidal concentration with Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis. Moreover, the most active derivative 13e exhibited a notable noncytotoxic effect on WI-38 cells revealing its safety. Finally, we have successfully synthesized nontoxic, antibacterial derivatives. Further research on these derivatives is possible to develop an effective antimicrobial drug.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2511-2522"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790687","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

Latest developments in small molecule inhibitors of cysteine protease B as antileishmanial drugs. 半胱氨酸蛋白酶B小分子抑制剂抗利什曼病的最新进展。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-07 DOI: 10.1080/17568919.2026.2714018

Karla Joane da Silva Menezes, Sonaly Lima Albino, João Vitor Vieira da Silva, Éric de Oliveira Rios, Rafaella Alves da Silva Barbosa, Juan D Rodríguez-Macías, Edgar Alexander Marquez Brazon, Fátima Nogueira, Sofia Cortes, Ricardo Olimpio de Moura, Igor José Dos Santos Nascimento

{"title":"Latest developments in small molecule inhibitors of cysteine protease B as antileishmanial drugs.","authors":"Karla Joane da Silva Menezes, Sonaly Lima Albino, João Vitor Vieira da Silva, Éric de Oliveira Rios, Rafaella Alves da Silva Barbosa, Juan D Rodríguez-Macías, Edgar Alexander Marquez Brazon, Fátima Nogueira, Sofia Cortes, Ricardo Olimpio de Moura, Igor José Dos Santos Nascimento","doi":"10.1080/17568919.2026.2714018","DOIUrl":"10.1080/17568919.2026.2714018","url":null,"abstract":"Leishmaniasis is a neglected tropical disease, transmitted by the bite of infected female sandflies and affecting the poor population. Current pharmacotherapy has remained largely unchanged for decades, and there are parasitic strains resistant to these conventional treatments. Thus, there is an urgent need to identify molecular targets to guide the rational design of new drugs. Thus, cysteine protease B (CPB) emerges as a promising target due to its roles in pathogenesis, virulence, and in modulating the host immune response. Given this potential, this review presents recent advances in CPB inhibitors, examining scaffolds, their structure-activity relationships (SARs), and the structural elements that confer selectivity for the parasitic target. Aziridine analogs and dipeptidyl nitriles stand out, and the SAR studies presented here indicate that structural modifications in the P1, P2, and P3 binding subsites influence compound affinity, thereby optimizing molecular fit in the enzyme. The stereochemical configuration (S,S) of the inhibitors is also essential for potency. Regarding selectivity, the Tyr210 residue is present in CPB but not in human cathepsin L. Taken together, these structural and mechanistic findings offer new perspectives for advancing medicinal chemistry targeting CPB, in the development of safer, more selective, and more effective antileishmanial agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2389-2402"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684016","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

Chalcone-indole hybrid scaffolds as promising anticancer drug candidates: a mini-review. 查尔酮-吲哚杂化支架作为有前途的抗癌候选药物：综述。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-20 DOI: 10.1080/17568919.2026.2714032

Yafei Zhuang, Yanjing Cheng, Danchen Zhao, Jun Yu, Lianlian Chen

{"title":"Chalcone-indole hybrid scaffolds as promising anticancer drug candidates: a mini-review.","authors":"Yafei Zhuang, Yanjing Cheng, Danchen Zhao, Jun Yu, Lianlian Chen","doi":"10.1080/17568919.2026.2714032","DOIUrl":"10.1080/17568919.2026.2714032","url":null,"abstract":"Cancer treatment is hampered by severe systemic side effects, poor tumor selectivity, and multidrug resistance (MDR). Molecular hybridization integrates chalcone and indole, two privileged antitumor pharmacophores, into one scaffold to generate chalcone-indole hybrids that synergistically enhance antitumor potency, improve tumor targeting, and reverse MDR. This mini-review analyzes literature from 2020 to 2026 on chalcone-indole anticancer hybrids. Based on structural modification patterns, the reported hybrids are categorized into four subgroups: simple substituted, α/β-position modified, N-1 fatty acid-substituted, and multi-pharmacophore fused hybrids. For each category, we summarize structure-activity relationships (SARs), antiproliferative activity, selective toxicity, molecular mechanisms, and in vivo xenograft performance. Most lead compounds exert tumor-suppressive effects via tubulin polymerization inhibition, G2/M cell cycle arrest, ROS overaccumulation, and mitochondrial-dependent apoptosis. Representative hybrids 10a, 12a, 21a, and 25a exhibit remarkable efficacy against drug-resistant colorectal, lung, and breast tumors with favorable in vivo safety. We highlight the application potential of different subtypes for specific malignancies, including α/β-modified analogues for resistant colorectal cancer, N-1 fatty acid-platinum conjugates for platinum-resistant lung cancer, NLRP3 inhibitor 7a for oral cancer, and multi-pharmacophore fused derivatives for broad-spectrum activity. Current bottlenecks limiting clinical transformation are discussed. This review provides structural design rules for developing novel chalcone-indole targeted anticancer agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2463-2476"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790684","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

Synthesis of benzenesulfonamide derivatives reveals anti-CCSCs activity by regulating Wnt/β-catenin pathway. 苯磺酰胺衍生物的合成通过调节Wnt/β-catenin通路揭示了抗ccscs的活性。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-09-03 DOI: 10.1080/17568919.2026.2726190

Xueyu Wang, Kaili Wang, Quanxing Zhong, Hao Yang, Yinan Zhang, Dong Wang, Yan Wu, Haijuan Qin, Baiwang Chu, Yiwen Duan, Peng Yu, Can Liu, Hua Sun

{"title":"Synthesis of benzenesulfonamide derivatives reveals anti-CCSCs activity by regulating Wnt/β-catenin pathway.","authors":"Xueyu Wang, Kaili Wang, Quanxing Zhong, Hao Yang, Yinan Zhang, Dong Wang, Yan Wu, Haijuan Qin, Baiwang Chu, Yiwen Duan, Peng Yu, Can Liu, Hua Sun","doi":"10.1080/17568919.2026.2726190","DOIUrl":"10.1080/17568919.2026.2726190","url":null,"abstract":"Background: Colorectal cancer (CRC) has become one of the most common causes of cancer mortality worldwide. Accumulating studies suggest that the progressive up-regulation of Wnt/β-catenin signaling is a crucial hallmark of CRC, and this pathway is involved in the development and maintenance of colorectal cancer stem cells (CCSCs). Therefore, inhibition of its activity may be an effective strategy for the treatment of CRC.Methods: Based on the reported structural characteristics of LF3 which is a small molecule inhibitor of β-catenin/Transcription Factor 4 (TCF4) and the significant role of the naphthoquinone group in anti-tumor activity, we designed and synthesized a series of benzenesulfonamide derivatives.Results: The results of anti-CRC activity showed that compound 3gg has anti-proliferation and anti-CCSCs activities by regulating the Wnt/β-catenin signaling pathway in vitro. In addition, compound 3gg could inhibit CCSCs activity through regulating the Wnt/β-catenin signaling pathway in xenografts.Conclusion: Compound 3gg, which inhibits CCSCs and Wnt/β-catenin signaling pathway activity, could be a promising lead compound for further investigation as a potential anti-cancer agent.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2477-2497"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886283","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

Design, synthesis and dual anticancer and antibacterial evaluation of novel 1,3,4-oxadiazole-2-thiol derivatives targeting EGFR and DNA Gyrase B: integrated docking, DFT and ADMET studies. 靶向EGFR和DNA Gyrase B的新型1,3,4-恶二唑-2-硫醇衍生物的设计、合成及其抗癌和抗菌双重评价：集成对接、DFT和ADMET研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-06 DOI: 10.1080/17568919.2026.2714027

Ila M Ram, Jay B Maheta, Darshna K Lakhnotra, Nargis H Shaikh, Prince A Dave, Parth Thakor, Shivani Lakhani, Anjali B Thakkar, Yogesh O Bhola

{"title":"Design, synthesis and dual anticancer and antibacterial evaluation of novel 1,3,4-oxadiazole-2-thiol derivatives targeting EGFR and DNA Gyrase B: integrated docking, DFT and ADMET studies.","authors":"Ila M Ram, Jay B Maheta, Darshna K Lakhnotra, Nargis H Shaikh, Prince A Dave, Parth Thakor, Shivani Lakhani, Anjali B Thakkar, Yogesh O Bhola","doi":"10.1080/17568919.2026.2714027","DOIUrl":"10.1080/17568919.2026.2714027","url":null,"abstract":"Novel 1,3,4-oxadiazole-2-thiol derivatives (8a-j) were synthesized via multistep reactions and characterized using IR, 1H NMR, and 13C NMR spectroscopy. The compounds were evaluated for dual anticancer and antibacterial activities through computational and experimental approaches. Molecular docking against EGFR (1M17) and DNA gyrase B (2XCT) revealed compound 8h as the most potent EGFR inhibitor (-7.528 kcal/mol), surpassing methotrexate (-7.448 kcal/mol), while compound 8c demonstrated superior DNA gyrase B binding (-7.263 kcal/mol), exceeding ciprofloxacin (-6.11 kcal/mol) by 19%. In vitro cytotoxicity against A549 human lung carcinoma cells identified compound 8c as the most active anticancer agent (IC50 = 14.59 ± 0.19 µg/mL), comparable to methotrexate (IC50 = 11.82 ± 1.22 µg/mL). Antibacterial screening against S. aureus, E. coli, and K. pneumoniae revealed compound 8d as the most effective broad-spectrum agent (MIC = 25 µg/mL across all strains), demonstrating 2-fold superior activity against S. aureus versus ciprofloxacin. Comprehensive DFT calculations on compound 8c elucidated frontier orbital energies (HOMO-LUMO gap: 4.7528 eV), global reactivity descriptors, optimized geometry, Mulliken charge distribution, and topological properties (MEP, RDG, ELF, LOL). ADMET profiling revealed favorable drug-likeness with 0-1 Lipinski violations, optimal lipophilicity (cLogP: 2.7-3.97), and good predicted oral absorption (57-64%). These findings establish 1,3,4-oxadiazole-2-thiol derivatives as promising dual-action therapeutic scaffolds.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2319-2335"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677712","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

Beyond the ATP-binding pocket: emerging strategies in kinase targeting from allosteric inhibition to targeted protein degradation. 超越atp结合口袋：从变构抑制到靶向蛋白降解的激酶靶向新策略。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-13 DOI: 10.1080/17568919.2026.2718758

Mei Zhou, Linshan Li, Xiaojuan Tang, Yazhu Zhao, Wei Zhang

{"title":"Beyond the ATP-binding pocket: emerging strategies in kinase targeting from allosteric inhibition to targeted protein degradation.","authors":"Mei Zhou, Linshan Li, Xiaojuan Tang, Yazhu Zhao, Wei Zhang","doi":"10.1080/17568919.2026.2718758","DOIUrl":"10.1080/17568919.2026.2718758","url":null,"abstract":"Protein kinases are central regulators of cellular signaling and remain a major target class in precision medicine. While ATP-competitive inhibitors-including conformation-selective and covalent agents-have delivered substantial clinical benefit, durable responses are frequently limited by the conservation of the ATP pocket and the emergence of resistance mutations (e.g. gatekeeper and solvent-front substitutions), as well as kinase noncatalytic functions that are not addressed by enzymatic inhibition alone. Consequently, kinase drug discovery is expanding beyond orthosteric occupancy toward modalities that reprogram kinase conformations or eliminate the target protein. This Review summarizes the structural and medicinal chemistry principles underlying (i) allosteric inhibition and (ii) proximity-induced degradation, with an emphasis on design logic, structure-activity relationships, and key liabilities in the beyond rule of five space. We further highlight enabling technologies-including structural biology, chemical proteomics, and AI/ML-assisted modeling-that support allosteric site identification, ternary complex engineering, and multi-parameter optimization. Finally, we discuss translational challenges for bifunctional molecules, including permeability, exposure-response relationships, off-target degradation, and safety, and propose practical considerations for developing next-generation selective kinase therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2445-2461"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759764","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

Design, synthesis, and biological evaluation of imidazole-triazole hybrids as dual antimicrobial and antioxidant agents: experimental and in silico studies. 咪唑-三唑复合物的设计、合成和生物学评价：实验和硅研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-19 DOI: 10.1080/17568919.2026.2718765

Ritika Chouhan, Vikas Verma, Sonia Rohilla, Ashwani Kumar, Meenakshi Bhatia, Vikramjeet Singh, Navneet Goyal, Amit Kumar

{"title":"Design, synthesis, and biological evaluation of imidazole-triazole hybrids as dual antimicrobial and antioxidant agents: experimental and in silico studies.","authors":"Ritika Chouhan, Vikas Verma, Sonia Rohilla, Ashwani Kumar, Meenakshi Bhatia, Vikramjeet Singh, Navneet Goyal, Amit Kumar","doi":"10.1080/17568919.2026.2718765","DOIUrl":"10.1080/17568919.2026.2718765","url":null,"abstract":"Background: Considering the growing challenge of antimicrobial resistance, novel imidazole-triazole hybrids were synthesized as promising antimicrobial and antioxidant candidates based on the pharmacological relevance of imidazole and triazole moieties.Materials and methods: The imidazole-triazole hybrid compounds were synthesized via Kornblum Oxidation, condensation reactions, and azide-alkyne cycloaddition, and their antimicrobial activity was assessed using a serial dilution assay.Results: Compound 5s showed strong antimicrobial activity against Escherichia coli, Bacillus subtilis, Candida albicans, and Rhizoctonia solani with MIC (Minimum inhibitory concentration) values of 0.0107, 0.0215, 0.0215, and 0.0423 μmol/mL, respectively, while 5o exhibited broad antibacterial activity and 5m demonstrated potent antifungal efficacy against most of the tested pathogens. Overall, the hybrids showed stronger activity against plant pathogens than animal pathogens, and 5b displayed significant antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, with an IC50 (half maximal inhibitory concentration) value of 0.0137 μmol/mL. Molecular docking showed that compound 5s strongly binds to sterol 14-α-demethylase and deoxyribonucleic acid (DNA) gyrase through hydrophobic, π-π stacking, and halogen interactions, indicating its potential as a promising antimicrobial lead.Conclusion: Among the synthesized hybrids, 5m, 5o, 5r, and 5s exhibited notable antimicrobial activity, suggesting their potential as promising leads for further optimization as novel antimicrobial agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2545-2561"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790712","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

Bis-thiosemicarbazone derivative as starting agent for synthesis of anti-breast cancer agents and targeting PIM-1 kinase. 双硫代氨基脲衍生物作为起始剂合成抗乳腺癌药物并靶向PIM-1激酶。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-09-10 DOI: 10.1080/17568919.2026.2726193

Alaa M Abu Alnjaa, Jihan Qurban, Eman M H Abbas, Hossa F Alshareef, Hanadi Y Medrasi, Amel S Younes, Thoraya A Farghaly

{"title":"Bis-thiosemicarbazone derivative as starting agent for synthesis of anti-breast cancer agents and targeting PIM-1 kinase.","authors":"Alaa M Abu Alnjaa, Jihan Qurban, Eman M H Abbas, Hossa F Alshareef, Hanadi Y Medrasi, Amel S Younes, Thoraya A Farghaly","doi":"10.1080/17568919.2026.2726193","DOIUrl":"10.1080/17568919.2026.2726193","url":null,"abstract":"Aims: To design, synthesize, and biologically evaluate novel bis-thiazole derivatives as potential PIM-1 kinase inhibitors for breast cancer therapy.Materials and methods: A series of new bis-thiazole derivatives were synthesized and evaluated for their antiproliferative activity against MDA-MB-231 and MCF-7 breast cancer cell lines. The most active compound 15c was further investigated for PIM-1 kinase inhibition, selectivity toward normal WI38 cells, apoptosis induction, and molecular interactions with the PIM-1 active site.Results and conclusion: Among the synthesized compounds, derivative 15c exhibited the highest antiproliferative activity against MDA-MB-231 and MCF-7 cells, with IC50 values of 2.17 and 1.46 μM, respectively. It demonstrated potent PIM-1 inhibitory activity (IC50 = 0.74 μM), a favorable selectivity index, and low toxicity toward WI38 cells. Furthermore, 15c significantly increased p53 and Bax levels by 6.8- and 6.2-folds, respectively, while reducing Bcl-2 levels to 0.34-fold relative to the control, indicating apoptosis induction. Molecular docking studies revealed strong binding interactions with key amino acid residues within the PIM-1 active site. Hence, compound 15c represents a promising PIM-1 kinase inhibitor with potent antiproliferative and pro-apoptotic activities, supporting its potential as a candidate for breast cancer treatment.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2563-2574"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929573","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