Future medicinal chemistry最新文献_第3页

Chromanone and chromone scaffolds in cancer and metabolic disorders: advances in synthesis, SAR, and developability (2020-2026). 癌症和代谢性疾病中的铬酮和铬酮支架：合成、SAR和可发展性的进展（2020-2026）。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-19 DOI: 10.1080/17568919.2026.2718762

Manisha Nidhar, Muhammad Afzal, Gaurav Gupta, Surya Nath Pandey, Vaishali Goel, Avijit Mazumder, Pavan Goud, Sachin Kumar Singh, Keshav Raj Paudel, Kamal Dua

{"title":"Chromanone and chromone scaffolds in cancer and metabolic disorders: advances in synthesis, SAR, and developability (2020-2026).","authors":"Manisha Nidhar, Muhammad Afzal, Gaurav Gupta, Surya Nath Pandey, Vaishali Goel, Avijit Mazumder, Pavan Goud, Sachin Kumar Singh, Keshav Raj Paudel, Kamal Dua","doi":"10.1080/17568919.2026.2718762","DOIUrl":"https://doi.org/10.1080/17568919.2026.2718762","url":null,"abstract":"Chromanone and chromone are related benzopyran-based scaffolds that offer multiple opportunities for structural modification and medicinal chemistry. This review summarizes studies published from 2020 to 2026 on the synthesis, structure-activity relationships, biological activities, and developability of these compounds in cancer and metabolic disorders. Recent synthetic approaches have enabled the modification of the heterocyclic ring, fused benzene ring, and carbonyl region, as well as the preparation of hybrid, fused, and spiro derivatives of these compounds. In anticancer research, these compounds have demonstrated antiproliferative, pro-apoptotic, cell cycle-modulating, and signaling-related effects. In metabolic disorders, the reported activities of these compounds include the inhibition of carbohydrate-digesting enzymes, improvement of insulin signaling, suppression of hepatic glucose production, and regulation of lipid metabolism. The review also evaluated the strength of the available evidence, noting that many studies remain limited to docking, isolated enzyme assays, or cell-based screening. The available information on physicochemical properties, pharmacokinetics, metabolism, safety, and in vivo efficacy is comparatively limited. Future research should prioritize standardized biological evaluations, robust mechanistic validations, and integrated optimization of potency, selectivity, safety, and pharmacokinetic properties to facilitate the translational development of chromanone- and chromone-based compounds.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-20"},"PeriodicalIF":3.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790670","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 : 2026-08-19 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":"https://doi.org/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":"1-17"},"PeriodicalIF":3.3,"publicationDate":"2026-08-19","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

Synthesis of polyhydroquinoline derivatives as potent antidiabetic and antioxidant agents: in vitro biological activities and computational studies. 作为有效抗糖尿病和抗氧化剂的聚对苯二酚衍生物的合成：体外生物活性和计算研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-15 DOI: 10.1080/17568919.2026.2718768

Sultan Muhammad, Abdul Latif, Aftab Alam, Mumtaz Ali, Ahmed A Elhenawy, Manzoor Ahmad, Shujaat Ahmad, Syed Adnan Ali Shah, Syahrul Imran, Farman Ali Khan

{"title":"Synthesis of polyhydroquinoline derivatives as potent antidiabetic and antioxidant agents: in vitro biological activities and computational studies.","authors":"Sultan Muhammad, Abdul Latif, Aftab Alam, Mumtaz Ali, Ahmed A Elhenawy, Manzoor Ahmad, Shujaat Ahmad, Syed Adnan Ali Shah, Syahrul Imran, Farman Ali Khan","doi":"10.1080/17568919.2026.2718768","DOIUrl":"https://doi.org/10.1080/17568919.2026.2718768","url":null,"abstract":"Aims: Diabetes mellitus (DM) is a severe metabolic disease characterized by increased blood glucose levels due to reduced insulin action or secretion. This study aimed to synthesize new polyhydroquinoline (PHQ)-based acyl hydrazide derivatives and assess their potential as dual inhibitors of α-amylase and α-glucosidase enzymes.Materials and methods: Various acyl hydrazide derivatives of PHQ were synthesized via a multi-step reaction and structurally deduced through modern spectroscopic techniques. These compounds were evaluated for their in vitro studies, while molecular docking was performed to gain mechanistic insights into their biological activities.Results and discussion: In the series, compound (2c) emerged as the most potent inhibitor against both enzymes (IC50 = 0.44 ± 0.07 µM and 0.17 ± 0.01 µM, respectively), showing greater efficacy than acarbose. Density functional theory (DFT) analysis revealed valuable insights into the electronic properties and showed the best correlation with the biological targets. Moreover, molecular docking analysis showed good binding interactions with the active sites of both enzymes, which was supported by the experimental activities.Conclusion: These integrated experimental and computational results demonstrate that the polyhydroquinoline scaffold represents a promising platform for developing next-generation antidiabetic therapeutics with enhanced efficacy and favorable safety profiles.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-22"},"PeriodicalIF":3.3,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764086","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

Harnessing the quinoline core for targeted cancer therapy. 利用喹啉核心进行靶向癌症治疗。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-13 DOI: 10.1080/17568919.2026.2718761

Cong-Jun Liu, Wei-Wen Huang, Jun-Jie Wang, Wen-Shuo Jiang, Xin-Yue Zhang, Xin Chen, Ya Gao, Xing-Jie Dai

引用次数: 0

Synthesis of thiosemicarbazone derivatives of thiophene-2-carboxylic acid as potent urease inhibitors: in vitro evaluation, molecular docking, and density functional theory analysis. 作为脲酶抑制剂的噻吩-2-羧酸硫代氨基脲酮衍生物的合成：体外评价、分子对接和密度泛函理论分析。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-07-13 DOI: 10.1080/17568919.2026.2699672

Wisal Khan, Laiba, Imtiaz Ahmad, Ahmed A Elhenawy, Syed Adnan Ali Shah, Ashwag S Alanazi, Abdul Shakoor, Aftab Alam, Momin Khan, Mohammed M Alanazi

{"title":"Synthesis of thiosemicarbazone derivatives of thiophene-2-carboxylic acid as potent urease inhibitors: in vitro evaluation, molecular docking, and density functional theory analysis.","authors":"Wisal Khan, Laiba, Imtiaz Ahmad, Ahmed A Elhenawy, Syed Adnan Ali Shah, Ashwag S Alanazi, Abdul Shakoor, Aftab Alam, Momin Khan, Mohammed M Alanazi","doi":"10.1080/17568919.2026.2699672","DOIUrl":"10.1080/17568919.2026.2699672","url":null,"abstract":"Aims: To synthesize and evaluate a series of thiosemicarbazone derivatives (2a-2g) incorporating thiophene-2-carboxylic acid as urease inhibitors.Materials and methods: The compounds were synthesized and characterized using modern spectroscopic techniques. In vitro urease inhibition was determined followed by computational analysis including docking, density functional theory (DFT), molecular dynamics simulations (MD), normal mode analysis (NMA), and SwissADME profiling. Compounds 2g, 2d, and 2b emerged as potent inhibitors with IC50 values of 5.48 ± 0.18 to 9.44 ± 0.32 µM, outperforming the reference thiourea (IC50 = 22.13 ± 2.82 µM). Structure-Activity Relationship (SAR) analysis revealed that electron-withdrawing nitro substituents at para positions dramatically enhanced inhibitory potency. Docking investigation demonstrated robust interactions with the urease active site that includes binuclear nickel center and residues His492, His519, and Asp633. DFT calculations established strong correlations between chemical reactivity indices and biological activity. Molecular docking and MD simulations validated stable binding interactions with key residues (His492, His519, and Asp633). NMA revealed enhanced flap flexibility (λ1 = 1.39 × 10-6) and motional coupling upon 2g binding.Conclusion: These results expose the synthesized compounds, especially 2g as a potent urease inhibitor and provide a valuable insight for future anti-urease drug development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2147-2159"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430271","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

Expanding the tetrazole space: medicinal chemistry, biological diversity and structure-activity relationships. 拓展四唑空间：药物化学、生物多样性和构效关系。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-18 DOI: 10.1080/17568919.2026.2688846

Anuradha Singampalli, Pardeep Kumar, Rani Bandela, Ankita Devi, Srinivas Nanduri, Venkata Madhavi Yaddanapudi

{"title":"Expanding the tetrazole space: medicinal chemistry, biological diversity and structure-activity relationships.","authors":"Anuradha Singampalli, Pardeep Kumar, Rani Bandela, Ankita Devi, Srinivas Nanduri, Venkata Madhavi Yaddanapudi","doi":"10.1080/17568919.2026.2688846","DOIUrl":"10.1080/17568919.2026.2688846","url":null,"abstract":"Tetrazole, a synthetic five-membered heterocycle composed of one carbon and four nitrogen atoms, has emerged as a privileged scaffold in modern drug discovery. Despite its absence in natural products, the tetrazole ring is widely recognized for its ability to function as a bioisostere of carboxylic acid and amides, offering improved metabolic stability, enhanced binding interactions, and favorable pharmacokinetic properties. A diverse array of tetrazole-based compounds has demonstrated potent biological activity, with several already approved for clinical use and many others under active investigation. These molecules have shown promise in the treatment of various diseases, including cancer, tuberculosis, diabetes, inflammatory conditions, infectious diseases, and neurodegenerative disorders. Ongoing structure-activity relationship (SAR) studies continue to drive the optimization of tetrazole derivatives for improved efficacy and reduced toxicity. Beyond therapeutic applications, tetrazoles are also being explored in advanced materials, catalysis, and agrochemical development. This review provides a comprehensive summary of recent progress in the synthesis, biological evaluation, and therapeutic potential of tetrazole-containing compounds, highlighting their significance in the rational design of next-generation drug candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2087-2105"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271044","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

Coumarin derivatives as antidiabetic agents: a comprehensive review on mechanistic insights, structure-activity relationships, in silico studies, and challenges. 香豆素衍生物作为抗糖尿病药物：机制见解，结构-活性关系，计算机研究和挑战的综合综述。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-22 DOI: 10.1080/17568919.2026.2688848

Salesh Verma, Sant Kumar Verma

{"title":"Coumarin derivatives as antidiabetic agents: a comprehensive review on mechanistic insights, structure-activity relationships, in silico studies, and challenges.","authors":"Salesh Verma, Sant Kumar Verma","doi":"10.1080/17568919.2026.2688848","DOIUrl":"10.1080/17568919.2026.2688848","url":null,"abstract":"In recent years, coumarin has been structurally modified by combining it with heterocyclic or other active pharmacophores such as thiazolidinedione, hydrazone, triazole, cinnamic acid, aza group, oxadiazole, sulfonamide, and piperidinyl to influence molecular targets related to diabetes, such as aldose reductase (ALR2), α-glucosidase, α-amylase, dipeptidyl peptidase-4 (DPP-4), peroxisome proliferator-activated receptor alpha (PPAR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), and protein tyrosine phosphatase 1B (PTP1B). This review provides a structured overview of the structure-activity relationship (SAR) of coumarin-based derivatives, focusing on their substitution patterns and functional relationships, which affect potency, selectivity, and efficacy. In silico analysis revealed key binding interactions between coumarin derivatives and the catalytic sites of different druggable enzyme targets. More progressive insights, including quantitative structure-activity relationship (QSAR) and machine learning, have been discussed, which have contributed to addressing the selectivity, solubility, safety, and stability challenges of these compounds. Moreover, this review highlighted coumarin hybrids as targeted candidates for future antidiabetic therapies.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2045-2068"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301487","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

Indole-based carbohydrazides as potent anti-proliferative leads and tubulin polymerization inhibitors: design, synthesis, cytotoxic evaluation, in silico ADMET and docking studies. 吲哚基碳肼作为有效的抗增殖导联剂和微管蛋白聚合抑制剂：设计、合成、细胞毒性评估、硅ADMET和对接研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-25 DOI: 10.1080/17568919.2026.2688854

Aisha A Alsfouk, Eman S Nossier, Mohamed A Omar, Marwa M Mounier, Hanaa S Mohamed, Alaadin E Sarhan, Asmaa Saleh, Aladdin M Srour

{"title":"Indole-based carbohydrazides as potent anti-proliferative leads and tubulin polymerization inhibitors: design, synthesis, cytotoxic evaluation, in silico ADMET and docking studies.","authors":"Aisha A Alsfouk, Eman S Nossier, Mohamed A Omar, Marwa M Mounier, Hanaa S Mohamed, Alaadin E Sarhan, Asmaa Saleh, Aladdin M Srour","doi":"10.1080/17568919.2026.2688854","DOIUrl":"10.1080/17568919.2026.2688854","url":null,"abstract":"Aims: A novel series of indolecarbohydrazide derivatives (3a-r) was designed and synthesized to evaluate their potential as tubulin polymerization inhibitors and selective anticancer agents.Materials and methods: The cytotoxic potential of compounds 3a-r was assessed against six human cancer cell lines and nonmalignant RPE-1 cells. Mechanistic studies included tubulin polymerization assays, cell cycle analysis, and apoptosis induction. Pharmacokinetic profiles were predicted using SwissADME, while molecular docking (MOE-Dock v2024.0601) explored binding affinities at the colchicine site.Results: Compounds 3b, 3d, 3i, and 3p showed significant potency against MCF-7 cells, with 3i being the most active (IC50 = 1.0 ± 0.05 mM), outperforming doxorubicin. Derivatives 3d and 3i effectively inhibited tubulin polymerization (IC50 = 3.96 and 6.28 μM, respectively), comparable to combretastatin A4. Compound 3d induced G2/M phase arrest and apoptosis, consistent with microtubule disruption. In silico analysis predicted favorable drug-like properties, and docking scores (-9.28 to -10.92 kcal/mol) confirmed high affinity for the colchicine binding site.Conclusions: These findings identify the indolecarbohydrazide scaffold as a potent anti-proliferative lead that successfully disrupts tubulin dynamics, offering a promising foundation for further development of colchicine-site microtubule-targeting agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2015-2029"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316620","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

Dual HDAC/PI3K inhibitors as a potential and emerging cancer therapy: a review. 双重HDAC/PI3K抑制剂作为潜在的和新兴的癌症治疗：综述。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-07-08 DOI: 10.1080/17568919.2026.2699690

Madhukumari, Akshatha Handattu Shankaranarayana, Salini P Nair, Arun Kumar S, Durgesh Bidye, Gurubasavaraj V Pujar

{"title":"Dual HDAC/PI3K inhibitors as a potential and emerging cancer therapy: a review.","authors":"Madhukumari, Akshatha Handattu Shankaranarayana, Salini P Nair, Arun Kumar S, Durgesh Bidye, Gurubasavaraj V Pujar","doi":"10.1080/17568919.2026.2699690","DOIUrl":"10.1080/17568919.2026.2699690","url":null,"abstract":"Cancer continues to cause a major global health challenge, largely because of the heterogeneity of molecular changes that allow cancer cells to grow uncontrollably and evade therapy. The various pathways implicated include HDACs and PI3Ks, which are key epigenetic regulators and intracellular signaling, as well as critical regulators of cell survival and proliferation. Once dysregulated, these pathways contribute to tumor initiation, disease progression, and resistance to currently used treatments. This review presents the biological roles, types, cellular localization, functional diversity, and roles in cancer progression of HDAC and PI3K family members. Further, discussed on the chemistry and SAR of FDA-approved HDAC, PI3K, and dual inhibitors with a special emphasis on the nature of the pharmacophore that affects potency, selectivity, and therapeutic activity. The review focuses on dual HDAC/PI3K inhibition as a single approach to simultaneously inhibit epigenetic regulation and pro-survival signaling in cancer cells. Dual inhibitors, such as CUDC-907 and BEBT-908, and their potential effectiveness in cytogenetic cancers and solid tumors; issues related to clinical trials; and future directions to enhance therapeutic outcomes are discussed. Currently, dual HDAC/PI3K inhibitors are an exciting next-generation anticancer agent that addresses the major drawbacks of existing therapies.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2257-2279"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410694","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

Thiazolidin-based dual Aurora kinase inhibitors with potent anticancer activity. 具有有效抗癌活性的噻唑烷基双极光激酶抑制剂。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-16 DOI: 10.1080/17568919.2026.2688748

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

{"title":"Thiazolidin-based dual Aurora kinase inhibitors with potent anticancer activity.","authors":"Walid E Elgammal, Hazem Elkady, Aisha A Alsfouk, Hazem A Mahdy, Dalal Z Husein, Fatma G Amin, Ibrahim H Eissa, Ahmed M Metwaly, Eslam B Elkaeed","doi":"10.1080/17568919.2026.2688748","DOIUrl":"10.1080/17568919.2026.2688748","url":null,"abstract":"Aims: To design, synthesize, and evaluate novel thiazolidin derivatives as potential dual inhibitors of Aurora kinases for anticancer therapy.Materials and methods: A series of thiazolidin derivatives was designed and evaluated for in vitro cytotoxic activity against HCT-116, MCF-7, HepG-2, and HeLa cancer cell lines. The most active compound was further investigated using kinase assays, cell cycle analysis, wound healing migration assays, and molecular dynamics simulations combined with Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) analysis.Results: Compound 11 exhibited potent antiproliferative activity with IC50 values of 0.32 ± 0.094 µM (HCT-116) and 0.15 ± 0.03 µM (MCF-7), with high selectivity indices of 242.5 and 517.0, respectively, compared with Vero cells (IC50 = 77.6 ± 1.8 µM). At the enzymatic level, compound 11 inhibited Aurora A and Aurora B with IC50 values of 0.23 and 0.91 µM, respectively, compared with Danusertib (0.13 and 0.25 µM), indicating comparable Aurora A inhibition. Compound 11 significantly reduced Aurora kinase levels, induced G2/M arrest, and triggered apoptosis. Molecular dynamics and MM-GBSA confirmed stable binding interactions.Conclusions: Compound 11 is a promising dual Aurora kinase inhibitor with potent anticancer activity and high selectivity, representing a valuable lead for further development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1947-1962"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257805","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