Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin

被引：99

作者：

Cui, Sheng-Feng ^{[1
]}

Peng, Li-Ping ^{[1
]}

Zhang, Hui-Zhen ^{[1
]}

Rasheed, Syed ^{[1
]}

Kumar, Kannekanti Vijaya ^{[1
]}

Zhou, Cheng-He ^{[1
]}

机构：

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

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 86卷

基金：

中国国家自然科学基金; 高等学校博士学科点专项科研基金;

关键词：

Quinolone; Metronidazole; Imidazole; DNA; Antibacterial; HSA; CALF THYMUS DNA; BIOLOGICAL EVALUATION; STRUCTURAL INSIGHT; RECENT RESEARCHES; AGENTS SYNTHESIS; DERIVATIVES; ANTIBACTERIAL; BERBERINE; DESIGN; PK(A);

D O I：

10.1016/j.ejmech.2014.08.063

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg2+ ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：318 / 334

页数：17

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