Novel Naphthalimide Aminothiazoles as Potential Multitargeting Antimicrobial Agents

被引：73

作者：

Chen, Ying-Ying ^{[1
]}

Gopala, Lavanya ^{[1
]}

Bheemanaboina, Rammohan R. Yadav ^{[1
]}

Liu, Han-Bo ^{[1
]}

Cheng, Yu ^{[1
]}

Geng, Rong-Xia ^{[1
]}

Zhou, Cheng-He ^{[1
]}

机构：

[1] Southwest Univ, Sch Chem & Chem Engn, Key Lab Appl Chem Chongqing Municipal, Inst Bioorgan & Med Chem, Chongqing 400715, Peoples R China

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Naphthalimide; aminothiazole; antibacterial; MRSA DNA; human serum albumin; HUMAN SERUM-ALBUMIN; CALF THYMUS DNA; BIOLOGICAL EVALUATION; BIOACTIVE EVALUATION; MEDICINAL CHEMISTRY; 2-AMINOTHIAZOLYL QUINOLONES; ANTIBACTERIAL ACTIVITY; DESIGN; DISCOVERY; HYBRIDS;

D O I：

10.1021/acsmedchemlett.7b00452

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative 4d displayed superior antibacterial activity against MRSA and Escherichia coli with MIC values of 4 and 8 mu g/mL, respectively, to reference drugs. The most active compound 4d showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations, revealed that compound 4d could not only bind with gyrase-DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form 4d-DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule 4d could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.

引用

页码：1331 / 1335

页数：5

共 32 条

[1] Design, synthesis, and biological evaluation of novel carbazole aminothiazoles as potential DNA-targeting antimicrobial agents [J].