Design, Synthesis, and Antimicrobial Evaluation of Novel Quinolone Imidazoles and Interactions with MRSA DNA. (16th March 2015)

• Record Type: Journal Article
• Authors: Zhang, Ling; Kumar, Kannekanti Vijaya; Rasheed, Syed; Geng, Rong‐Xia; Zhou, Cheng‐He
• Is Part Of: Chemical biology & drug design. Volume 86:Number 4(2015:Oct.)
• Page Start: 648
• Page End: 655
• Publication Date: 2015-03-16
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12532
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12532-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A novel series of quinolone imidazoles as new type of antimicrobial agents were synthesized. Most compounds exhibited good bioactivities especially against MRSA even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs and gave low cytotoxicity to human cells. The pKa values of these compounds showed appropriate ranges to pharmacokinetic behaviors. The interactions between compound <bold>8b</bold>, Cu²⁺ ion, and MRSA DNA revealed that compound <bold>8b</bold> could intercalate into DNA through copper ion bridge to form a steady <bold>8b</bold>–Cu²⁺–DNA ternary complex which might further block DNA replication to exert the powerful bioactivities. Study of compound <bold>8b</bold> with human serum albumin indicated that compound <bold>8b</bold> could be effectively stored and carried by human serum albumin.</p> </abstract>