Future medicinal chemistry最新文献_第8页

New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies. 靶向EGFR的新型噻唑烷-4- 1抗宫颈癌药物：设计、合成和计算研究

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1080/17568919.2024.2437976

Wafa A Bawazir, Nesreen S Ahmed, Somaia S Abd El-Karim, Ahmed F El-Sayed, Manal M Anwar

{"title":"New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies.","authors":"Wafa A Bawazir, Nesreen S Ahmed, Somaia S Abd El-Karim, Ahmed F El-Sayed, Manal M Anwar","doi":"10.1080/17568919.2024.2437976","DOIUrl":"10.1080/17568919.2024.2437976","url":null,"abstract":"Aim: A new series of 3,4-dihydronaphthalen-1(2 h)-ylidene)hydrazineylidene)-5-substituted thiazolidin-4-one derivatives were designed and synthesized.Results & methodology: The new compounds were screened for in vitro antitumor activity against Hela cancer cell line. The compounds 7b, 7 h, and 7i produced more potent cytotoxicity than doxorubicin with IC50 values of 1.83 ± 0.1, 2.54 ± 0.14, 2.75 ± 0.15, and 3.63 ± 0.2 μM, respectively. They also showed a promising safety profile against WI-38 normal cells. In addition, compound 7b produced a promising multi-kinase inhibition against EGFR (WT) while being very selective toward the mutant forms (L858R and T790M) with IC50 values of 0.099 ± 0.006, 0.064 ± 0.006, and 0.026 ± 0.007 μM, respectively, in comparison to gefitinib and osimertinib. A study of the cell cycle in Hela cells showed that 7b arrests cell cycle in the pre-G1 phase and causes early and late apoptosis. Eventually, the molecular docking results showed that 7b had good-binding interactions with EGFRWT, EGFRL858R, and EGFRT790M.Conclusion: Compound 7b was predicted to have promising oral absorption, good drug-likeness, and low toxicity risks in humans. Moreover, MD simulations confirmed the stable complexes of 7b with EGFRWT, EGFRL858R, and EGFRT790M (with RMSD 0.12-0.35 nm, RMSF 0.2-0.55 nm, SASA 140-150, and Rg 1.80-2.00 nm).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"75-91"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800166","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

Developing novel indoles as antitubercular agents and simulated annealing-based analysis of their binding with MmpL3. 开发新型抗结核药物吲哚及其与MmpL3结合的模拟退火分析。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-25 DOI: 10.1080/17568919.2024.2444872

Rajdeep Ray, Stutee Das, Sumit Raosaheb Birangal, Helena I Boshoff, Jose Santinni Roma, Manisha Lobo, Raghu Chandrashekhar Hariharapura, G Gautham Shenoy

{"title":"Developing novel indoles as antitubercular agents and simulated annealing-based analysis of their binding with MmpL3.","authors":"Rajdeep Ray, Stutee Das, Sumit Raosaheb Birangal, Helena I Boshoff, Jose Santinni Roma, Manisha Lobo, Raghu Chandrashekhar Hariharapura, G Gautham Shenoy","doi":"10.1080/17568919.2024.2444872","DOIUrl":"10.1080/17568919.2024.2444872","url":null,"abstract":"Aim: This research aimed to develop novel indole-2-carboxamides as potential antitubercular agents using rational drug design. It also focused on identifying the critical interactions required for these compounds to exhibit effective antitubercular activity.Materials and methods: Novel indole-2-carboxamides targeting MmpL3 were designed based on SAR, synthesized, and tested for their antitubercular and iniBAC induction properties. Classical docking and simulated annealing were utilized to understand protein-ligand binding affinity.Results: Compounds 5c, 5f, and 5i, were active against H37Rv and different MDR and XDR strains of M. tuberculosis. iniBAC promoter induction study indicated that those were inhibitors of MmpL3. Through the docking and simulated annealing studies, we identified key protein-ligand interactions at the MmpL3 binding site.Conclusion: We have identified three potent antitubercular molecules that supposedly act via inhibiting MmpL3. Results from the molecular modeling studies can be used in future drug designing.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"19-34"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885049","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

Novel coumarin linked pyrazoles, thiazoles, and thiadiazoles: synthetic strategies and in vitro antimicrobial investigation. 新型香豆素连接的吡唑、噻唑和噻二唑：合成策略和体外抗菌研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-26 DOI: 10.1080/17568919.2024.2444867

Salwa A Elsharabasy, Mariam T Sayed, Anhar Abdel-Aziem

{"title":"Novel coumarin linked pyrazoles, thiazoles, and thiadiazoles: synthetic strategies and in vitro antimicrobial investigation.","authors":"Salwa A Elsharabasy, Mariam T Sayed, Anhar Abdel-Aziem","doi":"10.1080/17568919.2024.2444867","DOIUrl":"10.1080/17568919.2024.2444867","url":null,"abstract":"Aim: Emerging resistance among pathogens necessitates the development of novel antimicrobial agents. As a result, we aimed to synthesize new coumarins and study their antimicrobial activity with the hope of obtaining effective drugs.Method: A series of coumarins were synthesized, characterized, and assessed for antimicrobial activity using broth microdilution and agar diffusion methods against Gram-positive (Bacillus pumilis, Streptococcus faecalis), Gram-negative (Escherichia coli, Enterobacter cloacae) bacteria, and fungi (Saccharomyces cerevisiae, Candida albicans).Results: Pyrazoles 15 and 16 revealed promising activities against all bacterial strains with MIC values ranging from 1.95 to 15.6 µg/ml. Notably, pyrazole 15 with CF3 in 3-position of pyrazole ring demonstrated higher ability to inhibit Streptococcus faecalis strain with MIC value equal to penicillin G (3.91 µg/ml). It also exhibited the best bactericidal potency against Escherichia coli with MBC value of 15.6 µg/ml while, pyrazole 16 recorded the same MBC value against Enterobacter cloacae. Pyrazole 15 demonstrated the strongest antifungal activity against both fungal strains with MIC and MFC values of 15.6, 7.81, 62.5, and 31.3 µg/ml against Saccharomyces cerevisiae and Candida albicans, respectively.Conclusion: These findings underscore the potential of coumarins, particularly compounds 15 and 16, as effective antimicrobial agents and provide critical insights into the design of bioactive molecules.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"183-193"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893453","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

Therapeutic targeting of neuroinflammation in methamphetamine use disorder. 甲基苯丙胺使用障碍患者神经炎症的靶向治疗。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-27 DOI: 10.1080/17568919.2024.2447226

Natasha Jeffery, Phooi Yan Mock, Kun Yang, Chau Ling Tham, Daud Ahmad Israf, Hongyuan Li, Xiaohui Wang, Kok Wai Lam

{"title":"Therapeutic targeting of neuroinflammation in methamphetamine use disorder.","authors":"Natasha Jeffery, Phooi Yan Mock, Kun Yang, Chau Ling Tham, Daud Ahmad Israf, Hongyuan Li, Xiaohui Wang, Kok Wai Lam","doi":"10.1080/17568919.2024.2447226","DOIUrl":"10.1080/17568919.2024.2447226","url":null,"abstract":"Methamphetamine (METH) is a highly addictive illicit psychostimulant with a significant annual fatality rate. Emerging studies highlight its role in neuroinflammation and a range of neurological disorders. This review examines the current landscape of potential drug targets for managing neuroinflammation in METH use disorders (MUDs), with a particular focus on the rationale behind targeting Toll-like receptor 4 (TLR4), the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and other promising targets. Given the multifactorial neurological effects of METH, including cognitive impairment and neurodegeneration, addressing METH-induced neuroinflammation has shown considerable promise in partially mitigating the damaging effects on the central nervous system and improving behavioral outcomes. This article provides an overview of the existing understanding while charting a promising path forward for developing innovative MUD treatments, focusing on neuroinflammation as a therapeutic target. Targeting neuroinflammation in METH-induced neurological disorders shows significant promise in mitigating cognitive impairment and neurodegeneration, offering a potential therapeutic strategy for improving outcomes in MUD. While challenges remain in optimizing treatments, ongoing research into combination therapies, novel drug delivery systems, and neuroprotective agents suggests a positive outlook for more effective interventions.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"237-257"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893493","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, characterization, and enzyme inhibition evaluation of sitagliptin derivatives and their metal complexes. 西格列汀衍生物及其金属配合物的合成、表征及酶抑制评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-31 DOI: 10.1080/17568919.2024.2447223

Javed Ahmed, Mohsin Abbas Khan, Saharish Khaliq, Anum Masood, Breena, Mashooq A Bhat, Muhammad Rizwan Khan, Asim Raza, Mohamed A Al-Omar, Farhat Ullah

{"title":"Synthesis, characterization, and enzyme inhibition evaluation of sitagliptin derivatives and their metal complexes.","authors":"Javed Ahmed, Mohsin Abbas Khan, Saharish Khaliq, Anum Masood, Breena, Mashooq A Bhat, Muhammad Rizwan Khan, Asim Raza, Mohamed A Al-Omar, Farhat Ullah","doi":"10.1080/17568919.2024.2447223","DOIUrl":"10.1080/17568919.2024.2447223","url":null,"abstract":"Aims: This study focuses on the synthesis and characterization of novel sitagliptin derivatives, aiming to develop potent, orally active anti-diabetic agents with minimal side effects for the management of type 2 diabetes mellitus. Copper (II) (SCu1-SCu9) and zinc (II) (SZn1-SZn9) metal complexes of sitagliptin-based derivatives were synthesized via a template reaction.Material & method: The synthesized complexes were comprehensively characterized using elemental analysis, FTIR, UV-Vis, 1 h NMR, and 13C NMR spectroscopy. The biological efficacy of these compounds was assessed through α-amylase and α-glucosidase enzyme inhibition assays, with molecular simulation studies providing additional confirmation of their inhibitory activity.Results: Among the tested derivatives, SD7, SD4, SD3, SD5, and SD9 demonstrated enzyme inhibition profiles comparable to the standard inhibitors. However, the metal complexes exhibited absorption challenges, which may influence their bioavailability.Conclusion: These findings highlight the significant anti-diabetic potential of the synthesized compounds against targeted enzymes, establishing a foundation for their development as lead molecules in future therapeutic research.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"195-207"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913968","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 the potential of the thioamide group in drug design and development. 释放硫胺类药物在药物设计和开发中的潜力。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1080/17568919.2024.2435245

Guang Huang, Tomasz Cierpicki, Jolanta Grembecka

引用次数: 0

Targeting undruggable protein KRAS for cancer therapy: novel opportunities and challenges. 靶向不可药物蛋白KRAS用于癌症治疗：新的机遇和挑战。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-23 DOI: 10.1080/17568919.2024.2444865

Xin Yang, Xiang Li, Yue-Lin Zhang, Sheng-Nan Zhang, Miao Zhang, Chong Sun, Li Yang, Hong-Min Liu, Shuo Yuan

引用次数: 0

Synthesis, DFT, ADMET and molecular docking studies of thiazole derived thiazolidinone-based chalcone derivatives: alzheimer's disease current therapies. 噻唑衍生噻唑烷酮类查尔酮衍生物的合成、DFT、ADMET及分子对接研究：阿尔茨海默病目前的治疗方法。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-04 DOI: 10.1080/17568919.2024.2421158

Muhammad Shahid Nadeem, Jalaluddin Azam Khan, Imran Kazmi, Ehssan Moglad, Muhammad Afzal, Sami I Alzarea, Fazal Rahim, Shoaib Khan, Khushi Muhammad, Gaurav Gupta

{"title":"Synthesis, DFT, ADMET and molecular docking studies of thiazole derived thiazolidinone-based chalcone derivatives: alzheimer's disease current therapies.","authors":"Muhammad Shahid Nadeem, Jalaluddin Azam Khan, Imran Kazmi, Ehssan Moglad, Muhammad Afzal, Sami I Alzarea, Fazal Rahim, Shoaib Khan, Khushi Muhammad, Gaurav Gupta","doi":"10.1080/17568919.2024.2421158","DOIUrl":"https://doi.org/10.1080/17568919.2024.2421158","url":null,"abstract":"Aim: Nitrogen and sulfur-containing compounds are the core components utilized for synthesis of different heterocyclic moieties.Methods & results: In this research, a series of new analogues containing thiazolidinone have been synthesized (1-20) in order to evaluate their activity against acetylcholinesterase and butyrylcholinesterase. Potent analogues were further subjected for molecular docking in order to study their protein-ligand interactions. The highly active analogues were also subjected for DFT, which confirmed the binding properties, electrical properties, and nature with the targeted enzyme. ADMET analysis also confirms the druglikeness properties of the synthesized series.Conclusion: Analog 5 (IC50 = 1.2 ± 0.1 µM and 1.8 ± 0.2 µM) exhibit excellent inhibition in comparison with the standard drug donepezil in view of inhibiting Alzheimer's disease.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767829","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

Environment benign synthesis of 5-acyl-4-hydroxypyridin-2(1H)-one derivatives as antioxidant and α-amylase inhibitors. 作为抗氧化剂和 α 淀粉酶抑制剂的 5-酰基-4-羟基吡啶-2(1H)-酮衍生物的无害环境合成。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1080/17568919.2024.2432289

Neelam Yadav, Ravi Kumar, Sarita Sangwan, Vidhi Dhanda, Anil Duhan, Jayant Sindhu

{"title":"Environment benign synthesis of 5-acyl-4-hydroxypyridin-2(1H)-one derivatives as antioxidant and α-amylase inhibitors.","authors":"Neelam Yadav, Ravi Kumar, Sarita Sangwan, Vidhi Dhanda, Anil Duhan, Jayant Sindhu","doi":"10.1080/17568919.2024.2432289","DOIUrl":"10.1080/17568919.2024.2432289","url":null,"abstract":"Aim: Oxidative stress, caused by postprandial activities, is a major global health issue causing chronic diseases like diabetes mellitus, cancer, and asthma. Therefore, it was envisaged to design and synthesize a series of substituted 4-hydroxypyridine-2(1 h)-ones in order to develop new molecules that can reduce oxidative stress and modulate α-amylase activity also.Materials & methods: An environmentally benign, solvent and catalyst free, natural product inspired synthesis of 4-hydroxypyridin-2(1 h)-one derivatives has been developed. The synthetic analogues were evaluated in vitro α-amylase activity and antioxidant potential.Results: Among all the synthesized compounds, 4a, 4c, and 4d displayed many folds higher antioxidants activity than the standard, BHT. The in vitro α-amylase inhibition was found to be moderate with IC50 values ranging from 5.48 to 9.31 mm as compared to the standard acarbose (IC50 = 0.65 mm). The most active compound against α-amylase 4c was further investigated for its binding affinity within the active site of the enzyme and the kinetics studies revealed probable uncompetitive mode of inhibition.Conclusion: Compound 4a was found to be promising antioxidant and 4c as a good α-amylase inhibitor. These compounds could pave the way for development of new α-amylase inhibitors with antioxidant capabilities thereby effectively mitigating diabetes mellitus.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2637-2646"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739045","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

Insights on exploring the therapeutic potential and structural modification of Tetrandrine. 探索四氢化萘的治疗潜力和结构改造的见解。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1080/17568919.2024.2432297

Liang Gong, He Liu, Bo Xu, Tao Yu, Yi Wang, Sheng-Li Niu, Rong Zeng, Qin Ouyang

{"title":"Insights on exploring the therapeutic potential and structural modification of Tetrandrine.","authors":"Liang Gong, He Liu, Bo Xu, Tao Yu, Yi Wang, Sheng-Li Niu, Rong Zeng, Qin Ouyang","doi":"10.1080/17568919.2024.2432297","DOIUrl":"10.1080/17568919.2024.2432297","url":null,"abstract":"Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid from Stephania tetrandra, is noted for its diverse pharmacological effects but faces limitations in clinical use due to toxicity, poor solubility, and low bioavailability. Researchers are working to address these issues by developing Tet derivatives with greater therapeutic potential through structural modification. Generally, key modifications include: 1) introducing an aromatic heterocycle or a hydrophobic alkyne unit at the C-5 position can enhance its antitumor activity; 2) adding an amide, sulfonamide, or electron-withdrawing group at the C-14 position can enhance its antitumor activity; 3) changing its structure to a quaternary ammonium salt can alter its solubility and greatly boost its antibacterial activity; 4) structural modification of the C-12-methoxybenzyl motif can enhance its metabolic stability and thus change the activity of the analogs; 5) Tet structural simplification may result in the identification of anticancer lead compounds with novel mechanisms of action. This review systematically summarizes these modification strategies and evaluates the biological activities of Tet derivatives, aiming to guide further optimization and facilitate the discovery of lead analogs with improved efficacy. The future direction and possibility of Tet structural optimization are also considered.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2687-2700"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739046","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