Identification of hydroxyphenyl cyanovinyl thiazoles as new structural scaffold of potential antibacterial agents

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-04-25 DOI:10.1016/j.bmcl.2025.130258

Xing Lu , Shao-Lin Zhang , Cheng-He Zhou

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Abstract

Unique hydroxyphenyl cyanovinyl thiazoles (HCTs) as new structural scaffolds of potential antibacterial agents were developed to overcome global increasingly serious drug resistance. Some synthesized HCTs could suppress the growth of the tested strains, especially, benzothiophenyl HCT 5c exhibited superior anti-Escherichia coli activity with a lower MIC of 0.5 μg/mL to norfloxacin (MIC = 1 μg/mL). The active benzothiophenyl HCT 5c displayed no obvious hemolysis, low cytotoxicity and a much lower trend for the development of drug-resistance than norfloxacin. Further exploration revealed that benzothiophenyl HCT 5c could intercalate to DNA to form a DNA–5c complex, which disturbed the biological functions to facilitate bacterial death. ADME analysis indicated that compound 5c possessed favorable druggability and promising pharmacokinetic properties. This work provided an insight into further developing hydroxyphenyl cyanovinyl thiazoles as new structural scaffold of promising antibacterial candidates.

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羟基苯基氰乙烯基噻唑作为新型结构支架的鉴定

为克服全球日益严重的耐药问题，羟基苯基氰胺基噻唑（hct）作为潜在的新型结构支架被开发出来。其中，苯并噻吩基HCT 5c具有较强的抗大肠杆菌活性，其抗大肠杆菌活性低于诺氟沙星（MIC = 1 μg/mL） 0.5 μg/mL。活性苯并噻吩HCT 5c溶血不明显，细胞毒性低，耐药趋势远低于诺氟沙星。进一步研究发现，苯并噻吩基HCT - 5c可嵌入DNA，形成DNA - 5c复合物，干扰生物功能，促进细菌死亡。ADME分析表明，化合物5c具有良好的药理作用和良好的药动学性质。这项工作为进一步开发羟基苯基氰乙烯基噻唑作为有前途的抗菌候选物的新结构支架提供了见解。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.