Future medicinal chemistry最新文献_第6页

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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557599/pdf/","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":"OA","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

Recent advances in the development of small molecule STK33 inhibitors. STK33小分子抑制剂的研究进展

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-23 DOI: 10.1080/17568919.2026.2688853

Dipti B Upadhyay, Mehul P Parmar, Hitendra M Patel

{"title":"Recent advances in the development of small molecule STK33 inhibitors.","authors":"Dipti B Upadhyay, Mehul P Parmar, Hitendra M Patel","doi":"10.1080/17568919.2026.2688853","DOIUrl":"10.1080/17568919.2026.2688853","url":null,"abstract":"The serine/threonine kinase 33 (STK33) has attracted attention in recent years as a synthetic-lethal partner of oncogenic KRAS, thereby representing a potential indirect route to target KRAS-driven cancers. Initially, RNAi screens suggested that STK33 inhibition might selectively kill KRAS-mutant cells. Over the past decade medicinal chemistry, structural biology, and pharmacology efforts have yielded a variety of small-molecule probes and inhibitor series directed at STK33. In this review, we provide a comprehensive analysis of the state-of-the-art in STK33 small-molecule inhibitor development: we examine the biology and regulation of STK33, target validation strategies, discovery approaches (HTSfragment-based, structure-based), major chemical classes (benzimidazoles, thiazoles, pyrimidines/quinazolines, covalent and natural-product-inspired scaffolds), structure-activity relationship (SAR) trends, in vitro and in vivo pharmacology, translational challenges (selectivity, redundancy, resistance, pharmacokinetics) and future directions. We critically discuss the apparently conflicting evidence on STK33's essentiality in KRAS-driven cancers, and argue for refined targeting strategies of STK33 (including degradation rather than simply kinase inhibition) alongside biomarker-guided patient stratification. With continued optimization of pharmacokinetics, selectivity, and mechanism of action, STK33 remains a promising, albeit challenging, target in precision oncology.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2031-2043"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301418","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

Oxazole-4,5-dicarboxylate derivatives as multifunctional targets against oral cancer and Streptococcus mutans oral pathogens. 恶唑-4,5-二羧酸衍生物作为口腔癌和变形链球菌口腔病原体的多功能靶点。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-07-11 DOI: 10.1080/17568919.2026.2699692

Tamilvelan Manjunathan, Ajay Guru

{"title":"Oxazole-4,5-dicarboxylate derivatives as multifunctional targets against oral cancer and Streptococcus mutans oral pathogens.","authors":"Tamilvelan Manjunathan, Ajay Guru","doi":"10.1080/17568919.2026.2699692","DOIUrl":"10.1080/17568919.2026.2699692","url":null,"abstract":"Aims: A mild and metal free method was employed for the synthesis of various substituted oxazoles (C1-C5). These compounds demonstrated the ability to quench ROS in an in vitro antioxidant assay. The biological studies were further expanded to evaluate the properties of these oxazole derivatives against oral pathogens and oral squamous cell carcinoma.Materials and methods: The antimicrobial activity was investigated against Streptococcus mutans oral pathogens using zone of inhibition and MIC assays. The interaction of the derivatives with the Antigen I/II carboxy-terminus receptor of S. mutans was studied. For anticancer studies, cytotoxic effects were evaluated. Network pharmacology experiments were conducted to identify the targets of C5 against oral cancer and gene expression analysis was performed.Results: Among the derivatives, C5 exhibited superior antimicrobial activity against S. mutans. The oxazole derivatives showed cytotoxic effects on oral squamous cell carcinoma. Gene expression analysis revealed that C5 enhanced the upregulation of Caspase-3, Caspase-8, and FasL.Conclusions: These findings emphasize that among the synthesized oxazole derivatives, C5 has better potential on promoting oral health through its antimicrobial and anticancer activities.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2127-2134"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420056","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

Investigation of the in silico, in vitro, and in vivo effects of a novel amino acid conjugate against DMBA-induced breast cancer in rats. 一种新型氨基酸偶联物对dba诱导的大鼠乳腺癌的体内、体外和体内作用的研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-06-13 DOI: 10.1080/17568919.2026.2688862

Muhammed Ismail Can, Abdullah Aslan, Kenan Koran, Harun Uslu, Can Ali Agca, Ibrahim Hanifi Ozercan, Ahmet Orhan Gorgulu

{"title":"Investigation of the in silico, in vitro, and in vivo effects of a novel amino acid conjugate against DMBA-induced breast cancer in rats.","authors":"Muhammed Ismail Can, Abdullah Aslan, Kenan Koran, Harun Uslu, Can Ali Agca, Ibrahim Hanifi Ozercan, Ahmet Orhan Gorgulu","doi":"10.1080/17568919.2026.2688862","DOIUrl":"10.1080/17568919.2026.2688862","url":null,"abstract":"This study aims to perform molecular docking analyses of a newly synthesized candidate compound and to investigate its therapeutic efficacy in vivo at an appropriate dose in a female rat model with induced breast cancer. To this end, the Cys-PA-Kum-OH compound (coumarin-containing cysteine amino acid conjugate) was synthesized for the first time within the scope of this study. The rats were divided into seven groups, each consisting of 12 animals. Following, molecular biological and histopathological analyses were conducted. As a result, MDA (malondialdehyde) levels decreased in the treatment groups, whereas CAT (catalase) and GSH (glutathione) levels significantly increased. Moreover, the expression levels of COX-2 (cyclooxygenase), HER2 (Human Epidermal Growth Factor Receptor), and TNF-α (Tumor necrosis factor) were downregulated in the treated groups, while p53 (Tumor protein) expression was upregulated. Histopathological examinations performed to assess tumor size and histological type revealed that invasive tumors were more prevalent in the damage (control) groups. In contrast, reduced tumor incidence and a significant decrease in tumor size were observed in the groups treated with the amino acid conjugate (AC) and tamoxifen (TAM). Based on these findings, the Cys-PA-Kum-OH conjugate exhibits protective properties against breast cancer, positioning it as a promising candidate for further investigation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1999-2014"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148250386","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

Unlocking new antimicrobial leads in the last decade: exploring quinolin-2-one based hybrids' synthesis, action, SAR, and challenges in tackling antimicrobial resistance. 解锁过去十年新的抗菌素线索：探索喹啉-2- 1基杂合物的合成、作用、SAR和应对抗菌素耐药性的挑战。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-08-01 Epub Date: 2026-07-13 DOI: 10.1080/17568919.2026.2699680

Mahmoud Alaaeldin Khattab, Mai I Shahin, Azza T Taher, Nermin Samir

{"title":"Unlocking new antimicrobial leads in the last decade: exploring quinolin-2-one based hybrids' synthesis, action, SAR, and challenges in tackling antimicrobial resistance.","authors":"Mahmoud Alaaeldin Khattab, Mai I Shahin, Azza T Taher, Nermin Samir","doi":"10.1080/17568919.2026.2699680","DOIUrl":"10.1080/17568919.2026.2699680","url":null,"abstract":"The rapid emergence of antimicrobial resistance (AMR) posed a major global health threat and created an urgent need for new broad-spectrum antimicrobial agents. The quinolin-2-one scaffold emerged as a privileged structural motif in medicinal chemistry because it exhibited promising activity against a wide range of bacterial and fungal pathogens. Continuous optimization of this scaffold remained essential to address the increasing burden of resistance. This review summarized recent advances in quinolin-2-one derivatives reported from 2015 to 2025. It systematically examined synthetic approaches and revealed a growing shift toward greener and more sustainable methodologies. The review also analyzed the structure-activity relationships that governed antimicrobial potency, integrated findings from biological evaluations, discussed proposed mechanisms of action, including inhibition of DNA topoisomerases and disruption of cell wall biosynthesis, and assessed the available toxicity data for the reported compounds. Advantages, disadvantages and future perspectives Quinolin-2-one derivatives demonstrated considerable therapeutic promise as versatile antimicrobial scaffolds. However, current studies revealed several limitations, including poor aqueous solubility, insufficient preclinical ADMET characterization, and limited in vivo validation. Future investigations should address these pharmacokinetic and toxicological limitations to support the rational design of next-generation quinolin-2-one hybrids and improve their potential for clinical translation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2227-2255"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430292","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