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Design, Synthesis, and Antibacterial Activity of Novel Pleuromutilin Derivatives Bearing an Amino Thiazolyl Ring
Author(s) -
Ling Yong,
Wang Xinyang,
Wang Hui,
Yu Jianghe,
Tang Junming,
Wang Donggeng,
Chen Guangtong,
Huang Jinhua,
Li Yuqin,
Zheng Heng
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100430
Subject(s) - antibacterial activity , chemistry , docking (animal) , stereochemistry , bacteria , combinatorial chemistry , ring (chemistry) , antibiotics , biochemistry , organic chemistry , biology , medicine , genetics , nursing
A series of novel pleuromutilin derivatives containing the amino thiazolyl ring were designed, synthesized, and evaluated for their antibacterial activities in vitro against Gram‐positive clinical bacteria. All the target compounds showed better aqueous solubility compared with the lead compound ( 10 ). Most compounds displayed strong antibacterial activities against both susceptible and resistant bacteria, particularly for the compound ( 12f ) which showed extraordinary antibacterial properties superior to amoxicillin and tiamulin. Molecular docking studies revealed that the amino thiazolyl ring, the side chains of the pleuromutilin derivatives, can be adopted in the binding pocket of the 50S ribosomal subunit near the mutilin core. Therefore, our novel findings may provide new insights into the design of novel pleuromutilin derivatives and lay the basis for further studies on these promising antibiotics for human clinical use.