Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11,12-cyclic carbonate ketolides

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• 作者：Jian-Hua Liang^a ; ¹ ; ^{ljhbit@bit.edu.cn} ; Kun An^a ; Wei Lv^b ; Mark Cushman^b ; ² ; ^{cushman@purdue.edu} ; He Wang^c ; Ying-Chun Xu^c
• 关键词：Erythromycin ; Multi-drug resistance ; Ketolide ; Antibacterial activity ; Macrolide ; Oxime
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：59
• 期：Complete
• 页码：54-63
• 全文大小：707 K

文摘

A series of 9-O-(3-aryl-2-propargyl)oxime ketolides 8 was synthesized and evaluated for in?vitro antibacterial activity. Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLS_B-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin. Especially, 8i (Ar4-isoquinolyl) possessed an MIC of 0.064?¦Ìg/mL against constitutively MLS_B-resistant Streptococcus pneumoniae, and MICs of 0.032-0.064?¦Ìg/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis. The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers. A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9.