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

IF 3.4 4区医学 Q3 CHEMISTRY, MEDICINAL 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":null,"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":3.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834423/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2025.2463869","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

基于非葡萄糖苷的1,3,4-噻二唑类SGLT-2抑制剂的设计、合成及生物学评价

目的：2型糖尿病（T2DM）是一种需要胰岛素独立治疗的主要代谢性疾病；本研究开发了希夫碱1,3,4-噻二唑作为葡萄糖共转运蛋白2 （SGLT2）抑制剂。材料与方法：合成目标化合物，对接研究，体外和体内分析。结果：sss6和sss2在体外抑制SGLT2的活性分别为78.57%±2.8和74.60%±1.12，而相同剂量的达格列净的抑制活性为93.65%±4.48。体内实验结果显示，与达格列净（775±32.68 mg/体重）相比，sss2显著改善了尿糖的排泄（854±46.51 mg/体重）。与达格列净（158±15.9 mg/dL）相比，sss6和sss2显著降低血糖水平（137±4.89 mg/dL和183±15.07 mg/dL）。结论：化合物sss6和sss2作为SGLT2抑制剂治疗T2DM的潜在候选物有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.