Novel sulfonyl hydrazide based β-carboline derivatives as potential α-glucosidase inhibitors: design, synthesis, and biological evaluation.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2024-08-14 DOI:10.1007/s11030-024-10943-4

Jinping Sun, Di Xiao, Ming Lang, Xuetao Xu

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引用次数: 0

Abstract

A series of novel sulfonyl hydrazide based β-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC₅₀ values being 2.12 ± 0.33-19.37 ± 1.49 μM. Compound SX29 with a para-phenyl (IC₅₀: 2.12 ± 0.33 μM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 μM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based β-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.

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新型磺酰肼基 β-咔啉衍生物作为潜在的 α-葡萄糖苷酶抑制剂：设计、合成和生物学评价。

设计并合成了一系列新型磺酰肼基 β-咔啉衍生物（SX1-SX32），并通过核磁共振和 HRMS 对其结构进行了表征。其α-葡萄糖苷酶抑制筛选结果表明，化合物（SX1-SX32）具有潜在的α-葡萄糖苷酶抑制作用：IC50 值为 2.12 ± 0.33-19.37 ± 1.49 μM。具有对位苯基的化合物 SX29 的活性最强（IC50：2.12 ± 0.33 μM），被确认为非竞争性抑制剂。研究人员通过荧光光谱、CD光谱和分子对接来描述 SX29 对α-葡萄糖苷酶的抑制机制。细胞毒性表明，SX29（0-32 μM）对 293T 细胞无细胞毒性。体内实验表明，口服 SX29 能调节糖尿病小鼠的高血糖和葡萄糖耐量。这些研究结果表明，磺酰肼基 β-咔啉衍生物具有发现具有降糖活性的新型 α-葡萄糖苷酶抑制剂的潜力。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;