European Journal of Medicinal Chemistry (2020)
Update date:2022-08-15
Topics:
Zhang, Zhe
Li, Kang
Zhang, Guang-Yu
Tang, You-Zhi
Jin, Zhen
A series of novel pleuromutilin derivatives possessing 1,2,3-triazole moieties were synthesized via click reactions under mild conditions. The in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD 3, and 144) and 1 strain of E. coli (ATCC 25922) were tested by the broth dilution method. The majority of the synthesized derivatives displayed potent antibacterial activities against MRSA (MIC = 0.125–2 μg/mL). It was also found that most compounds had no significant inhibitory effect on the proliferation of RAW264.7 cells at the concentration of 8 μg/mL. Among these derivatives, compound 32 (~1.71 log10 CFU/g) containing dimethylamine group side chain displayed more effective than tiamulin (~0.77 log10 CFU/g) at the dose of 20 mg/kg in reducing MRSA load in thigh infected mice. Additionally, compound 32 (the survival rate was 50%) also displayed superior in vivo efficacy to that of tiamulin (the survival rate was 20%) in the mouse systemic model. Structure-activity relationship (SAR) studies resulted in compound 32 with the most potent in vitro and in vivo antibacterial activity among the series. Moreover, compound 32 was evaluated in CYP450 inhibition assay and showed moderate in vitro inhibition of CYP3A4 (IC50 = 6.148 μM).
View MoreWeifang Dongxing Chitosan Factory
website:http://dxchitosan.lookchem.com/
Contact:13475651157
Address:Weifang city ,shandong province
ClickChem Technology Co., Limited
Contact:+86-0310-6519966/0531-52893837
Address:No.750 Shunhua Road, High-Tech Zone, Jinan city, Shandong China
ALPHA PHARMACEUTICAL CO,LTD JIANGSU
Contact:+86-527-84829968,+86-527-84829998
Address:suqian city
YanCheng LongShen Chemical Co.,Ltd.
Contact:+86-515-86668866
Address:No.13,Weiyi Road,Funing Aoyang Industrial Park
Contact:+86-18653358619
Address:zibo
Doi:10.1016/j.bmc.2017.09.022
(2017)Doi:10.1021/jo982342h
(1999)Doi:10.1016/S0040-4020(01)81309-0
(1989)Doi:10.1590/S0103-50532010000200014
(2010)Doi:10.1021/ol1019508
(2010)Doi:10.1055/s-0037-1609448
(2018)