3D-QSAR and molecular docking for the discovery of ketolide derivatives.

Zhi-Xiong Ruan, De-Sheng Huangfu, Xing-Jun Xu, Ping-Hua Sun, Wei-Min Chen

Jinan University, College of Pharmacy, Department of Medicinal Chemistry, Guangzhou, P.R. China.

Expert opinion on drug discovery 2013 Apr

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There is an urgent need to discover novel antibiotics to overcome the growing problem of antibiotic resistance, which has become a serious concern in current medicine. Ketolides, the third generation of macrolide antibiotics, have shown promising effect against macrolide-resistant pathogens in respiratory diseases. Currently, a number of ketolide derivatives with excellent antibacterial activities have been reported, while their structure-activity relationships (SARs) were rarely explored systematically. Computer-aided drug design (CADD) such as 3D-QSAR and molecular docking are useful tools to study drug SARs in medicinal chemistry. Using these technologies, ketolide derivatives were systemically analyzed revealing important useful information about their SARs, providing useful information which can guide new drug design and optimization. The authors provide an overview of the currently reported 3D-QSAR models of ketolide derivatives. The authors present a comprehensive SAR model obtained from in-depth 3D-QSAR and molecular docking analysis for all kinds of ketolide derivatives. 3D-QSAR has been shown to be a reliable tool that had successfully assisted the design of several new antibiotics with improved activity and reduced toxicity. By applying 3D-QSAR and molecular docking, a comprehensive and systematic SAR model for ketolide derivative discovery was formed, which is important to guide future drug design for the discovery of better ketolides with lower toxicity.

Citation

Zhi-Xiong Ruan, De-Sheng Huangfu, Xing-Jun Xu, Ping-Hua Sun, Wei-Min Chen. 3D-QSAR and molecular docking for the discovery of ketolide derivatives. Expert opinion on drug discovery. 2013 Apr;8(4):427-44