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

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

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

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

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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.

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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.