Synthesis and antibacterial evaluation of 13-substituted cycloberberine derivatives as a novel class of anti-MRSA agents

European Journal of Medicinal Chemistry
Tian-Yun FanDan-Qing Song

Abstract

A series of new 13-substituted cycloberberine (CBBR) derivatives were prepared and evaluated for their antibacterial activities against Gram-positive bacteria taking CBBR as the lead. Structure-activity relationship revealed that the introduction of a suitable electron-donating group at the 13-position in CBBR might be beneficial for the antibacterial potency. Among them, compounds 5b and 5w exhibited high potency against methicillin-sensitive (MSSA) and resistant strains of S. aureus (MRSA) with MIC values of 1-4 μg/mL. Both of them also displayed high stabilities in blood, and good in vivo safety profiles with LD50 values of 65.6 and 41.2 mg kg-1 in intravenous route respectively. Molecular docking analysis indicated that compound 5b might target FtsZ protein that could inhibit cell division, with the advantage of activity against multidrug resistant S. aureus. Therefore, we consider 13-substituted CBBR derivatives to be a novel class of anti-MRSA agents worthy of further investigation.

Citations

Mar 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tianyun FanDanqing Song
Mar 14, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuan-Shuai YangDan-Qing Song
Jul 19, 2020·The FEBS Journal·Huihui HanJianhua Wang
Feb 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tianyun FanDanqing Song

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