Future medicinal chemistry最新文献_第3页

Camptothecin: a key building block in the design of anti-tumor agents.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-25 DOI: 10.1080/17568919.2025.2458455

Bowen Liu, Lei Yao

引用次数: 0

Pioneering first-in-class HDAC-ROCK inhibitors as potential multitarget anticancer agents.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1080/17568919.2025.2459589

Milan Beljkas, Dusan Ruzic, Ana Djuric, Ana Vuletic, Guilaine Nchugoua Tchiehe, Corinne Jallet, Véronique Cadet-Daniel, Paola B Arimondo, Juan F Santibanez, Tatjana Srdic-Rajic, Katarina Nikolic, Slavica Oljacic, Milos Petkovic

{"title":"Pioneering first-in-class HDAC-ROCK inhibitors as potential multitarget anticancer agents.","authors":"Milan Beljkas, Dusan Ruzic, Ana Djuric, Ana Vuletic, Guilaine Nchugoua Tchiehe, Corinne Jallet, Véronique Cadet-Daniel, Paola B Arimondo, Juan F Santibanez, Tatjana Srdic-Rajic, Katarina Nikolic, Slavica Oljacic, Milos Petkovic","doi":"10.1080/17568919.2025.2459589","DOIUrl":"10.1080/17568919.2025.2459589","url":null,"abstract":"Aim: With the aim of simultaneously modulating the epigenetic system and the protein kinase pathway, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases (ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimetastatic properties. We report here the rational design, synthesis, and biological evaluation of the first-in-class HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).Materials and methods: A molecular docking study performed with the Gold software was used to develop HDAC/ROCK multitarget inhibitors. IC50 values were determined by enzyme assays. The cytotoxicity, anti-migratory and anti-invasive properties of the inhibitors were evaluated using triple-negative breast cancer cells (MDA-MB-231 and HCC 1973) and pancreatic ductal adenocarcinoma cells (Panc-1 and MiaPaCa-2).Results: C-9 showed significant inhibition of HDAC6, ROCK1 and ROCK2. At the same time, this compound showed strong antiproliferative effects on MDA-MB-231, MiaPaCa-2 and Panc-1 cell lines with IC50 values of 5.81 μM, 3.87 μM and 19.57 μM. In addition, it demonstrated great anti-invasive and anti-migratory effects.Conclusion: The findings of this study strongly suggest that the simultaneous inhibition of ROCK and HDACs holds significant potential as a promising therapeutic strategy in the advancement of cancer treatment.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"393-407"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064644","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

Therapeutic potential of chalcone-1,2,3-triazole hybrids as anti-tumour agents: a systematic review and SAR studies.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-31 DOI: 10.1080/17568919.2025.2458450

Sakshi Priya, Md Mustahidul Islam, Shivani Kasana, Balak Das Kurmi, Ghanshyam Das Gupta, Preeti Patel

{"title":"Therapeutic potential of chalcone-1,2,3-triazole hybrids as anti-tumour agents: a systematic review and SAR studies.","authors":"Sakshi Priya, Md Mustahidul Islam, Shivani Kasana, Balak Das Kurmi, Ghanshyam Das Gupta, Preeti Patel","doi":"10.1080/17568919.2025.2458450","DOIUrl":"10.1080/17568919.2025.2458450","url":null,"abstract":"The study of chalcone-1,2,3-triazole hybrids for anticancer activity is quite a recent area of focus, primarily because of the increasing demand for developing new drugs to treat cancer. The chalcones and 1,2,3-triazole rings in hybrid compounds has recently emerged as a promising strategy for developing novel anticancer agents. The 1,2,3-triazole ring, known for its stability and hydrogen bonding capabilities, enhances the target binding affinity of these hybrids. Chalcones possess an α,β-unsaturated carbonyl system crucial for their anticancer activity The synergistic effect of these two moieties results in compounds with potent anticancer properties. This review explores the structure-activity relationship studies which revealed that the electronic and lipophilic properties of substituents on the phenyl rings of chalcones significantly influence their anticancer activity. Electron-donating and electron-withdrawing groups can affect cellular uptake and target engagement. Incorporating various substituents into the 1,2,3-triazole ring can improve selectivity and potency against specific cancer cell lines. These hybrids often exert their anticancer effects through apoptosis and cell cycle disruption. Recent research indicates 1,2,3-triazole chalcone hybrids hold therapeutic promise as anticancer agents. Further optimization through SAR studies and in-depth mechanistic investigations could lead to the development of highly potent and selective anticancer agents with minimal toxicity.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"449-465"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064736","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

The antimicrobial activity of auranofin and other gold complexes. 金糠蛋白及其它金配合物的抗菌活性。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.1080/17568919.2025.2453422

Xiuli Chen, Lin Lv, Shuang Wei, Wukun Liu

引用次数: 0

Design, synthesis and biological evaluation of non-glucosidal based 1,3,4-thiadiazoles as SGLT-2 inhibitors.

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-02-11 DOI: 10.1080/17568919.2025.2463869

Shivani Sharma, Shubham Kumar, Jeena Gupta, Amit Mittal, Navneet Khurana

{"title":"Design, synthesis and biological evaluation of non-glucosidal based 1,3,4-thiadiazoles as SGLT-2 inhibitors.","authors":"Shivani Sharma, Shubham Kumar, Jeena Gupta, Amit Mittal, Navneet Khurana","doi":"10.1080/17568919.2025.2463869","DOIUrl":"10.1080/17568919.2025.2463869","url":null,"abstract":"Aim: Type-2 diabetes mellitus (T2DM) is a major metabolic disorder needing insulin-independent treatments; this study developed Schiff base 1,3,4-thiadiazole as Sodium Glucose Co-transporters 2 (SGLT2) inhibitors.Materials and methods: The target compounds were synthesized followed by docking studies, in vitro and in vivo analysis.Results: In vitro assay revealed SSS 6 and SSS 2 exhibited high SGLT2 inhibition activity i.e. 78.57% ± 2.8 and 74.60% ± 1.12 compared to dapagliflozin (93.65% ± 4.48) at same dosage in enzyme inhibition assays. In vivo results reveals that SSS 2 significantly improved excretion of urinary glucose (854 ± 46.51 mg/body weight) as compared to dapagliflozin (775 ± 32.68 mg/body weight. SSS 6 and SSS 2 significantly decreased blood glucose levels (137 ± 4.89 mg/dL and 183 ± 15.07 mg/dL) relative to dapagliflozin (158 ± 15.9 mg/dL).Conclusion: Compounds SSS 6 and SSS 2 emerge as a potential candidates for further investigation as SGLT2 inhibitors for treating T2DM.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"409-423"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398438","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

Key molecular scaffolds in the development of clinically viable α-amylase inhibitors. α-淀粉酶抑制剂开发中的关键分子支架。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-21 DOI: 10.1080/17568919.2025.2453421

Rahul Singh, Jayant Sindhu, Devender Singh, Parvin Kumar

{"title":"Key molecular scaffolds in the development of clinically viable α-amylase inhibitors.","authors":"Rahul Singh, Jayant Sindhu, Devender Singh, Parvin Kumar","doi":"10.1080/17568919.2025.2453421","DOIUrl":"10.1080/17568919.2025.2453421","url":null,"abstract":"The escalating cases of type II diabetes combined with adverse side effects of current antidiabetic drugs spurred the advancement of innovative approaches for the management of postprandial glucose levels. α-Amylase is an endoamylase responsible for the breakdown of internal α-1,4-glycosidic linkages in dietary starch, producing oligosaccharides. Subsequently, α-glucosidase degraded these oligosaccharides to monosaccharides, which are absorbed into the bloodstream and become available to the body. The inhibitors of α-amylase reduced the digestibility of carbohydrates accompanied by delayed glucose absorption, leading to decreased blood glucose levels after meals and thus, inhibition of the enzyme seems to be a crucial strategy for diabetes management and improving overall glycemic control in diabetic patients. The present review article emphasizes the therapeutic promise of recently discovered potential α-amylase inhibitors, highlighting their in vitro, in silico and in vivo profiles. Ultimately, we addressed the contemporary challenges and potential routes ahead in the search for safe and reliable α-amylase inhibitors for clinical use, summarizing the most recent research in the field.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"347-362"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003324","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

PROTACs in the treatment of viral diseases. PROTACs在病毒性疾病治疗中的应用。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.1080/17568919.2025.2453418

Ritesh P Bhole, Payal Kute, Shilendra S Gurav

引用次数: 0

Advances in antitumor effects of pterostilbene and its derivatives. 紫檀芪及其衍生物抗肿瘤作用研究进展。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1080/17568919.2024.2435251

Xin Yu, Mengzhen Xu, Ziye Gao, Haixing Guan, Qingjun Zhu

引用次数: 0

Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation. 新型双苯并咪唑-三唑杂交体：抗癌研究、计算机方法和机制研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-13 DOI: 10.1080/17568919.2024.2437980

Moataz A Soliman, Hany E A Ahmed, Elsayed H Eltamany, Ahmed T A Boraei, Ateyatallah Aljuhani, Samir A Salama, Read Alghamdi, Ahmed K B Aljohani, Mohammed Almaghrabi, Mohamed R Aouad

{"title":"Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation.","authors":"Moataz A Soliman, Hany E A Ahmed, Elsayed H Eltamany, Ahmed T A Boraei, Ateyatallah Aljuhani, Samir A Salama, Read Alghamdi, Ahmed K B Aljohani, Mohammed Almaghrabi, Mohamed R Aouad","doi":"10.1080/17568919.2024.2437980","DOIUrl":"10.1080/17568919.2024.2437980","url":null,"abstract":"Aim: Benzimidazole-triazole conjugates are very active hotspot for design and synthesis of promising anticancer agents. The target analogs showed potent and selective cytotoxicity over different cancer cell lines for breast and lung ones.Materials & methods: A new series of bis-1,4-disubstituted-1,2,3-triazoles moieties conjugated with a 2-mercapto-benzimidazole 4a-h and 7a-g was synthesized via the click cycloaddition (CuAAC) reaction. The synthesized triazoles were characterized using several spectroscopic tools. In addition, they were tested against variable cell lines representing different cancer types; HepG-2, MCF-7, HCT-116, and A-549. Computational experiments were introduced for understanding their structure-activity relationships.Results & conclusion: The data revealed the outperformance of 7a-g analogs over 4a-h one with very effective IC50 values; 4-13 µg/mL compared to the reference drugs. Moreover, detailed mechanistic analyses showed potent Aurora-A Kinase expression for the most active analogs 7a and 7d exhibiting IC50; 3.5 and 5.3 over the control cells 8 ng/mL respectively. Additionally, based on their Aurora-A Kinase inhibitory activity, compound 7a was promising in apoptosis induction and cell cycle arrest. Molecular docking studies with Aurora-A Kinase revealed binding behaviors similar to the co-crystallized ligand sunitinib. Finally, this scaffold exhibits cytotoxic activity via apoptosis, enzyme downregulation, and suppression of cell division.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"93-107"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817736","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 and antimicrobial activity evaluation of pyrazole derivatives containing imidazothiadiazole moiety. 含咪唑噻二唑类吡唑衍生物的合成及抗菌活性评价。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-26 DOI: 10.1080/17568919.2024.2444868

Lan-Ying Han, Jing-Xin Sun, Chuang Liu, Bing Ai, Ming-Guan Piao, Changhao Zhang, Ji-Shan Quan, Cheng-Hua Jin

{"title":"Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing imidazothiadiazole moiety.","authors":"Lan-Ying Han, Jing-Xin Sun, Chuang Liu, Bing Ai, Ming-Guan Piao, Changhao Zhang, Ji-Shan Quan, Cheng-Hua Jin","doi":"10.1080/17568919.2024.2444868","DOIUrl":"10.1080/17568919.2024.2444868","url":null,"abstract":"Aim: The purpose of this work was to investigate the antimicrobial activity of pyrazole derivatives (21a - i and 23a - o) synthesized.Materials & methods: The pyrazole derivatives were synthesized, molecular docked and tested for their antimicrobial activity, cytotoxicity, and hemolysis rate.Results: Most of the target compounds showed high selective inhibitory activity against multi-drug resistance compared with other strains. Of these, compounds 21c (MIC = 0.25 µg/mL) and 23 h (MIC = 0.25 µg/mL) showed the strongest antibacterial activity, which was 4-flods than that of the positive control compound gatifloxacin (MIC = 1 µg/mL). Furthermore, compound 23 h showed no cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration.Conclusion: These results prompted that these compounds are valuable for further development as antimicrobial agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"157-170"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893488","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