Premium
Antibacterial Activity and Structure−Activity Relationship of a Series of Newly Synthesized Pleuromutilin Derivatives
Author(s) -
Li YunGe,
Wang JuXian,
Zhang GuoNing,
Zhu Mei,
You XueFu,
Hu XinXin,
Zhang Fan,
Wang YuCheng
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201800560
Subject(s) - moiety , chemistry , thioether , antibacterial activity , sulfoxide , antimicrobial , structure–activity relationship , combinatorial chemistry , stereochemistry , in vitro , organic chemistry , biochemistry , bacteria , genetics , biology
A series of novel thioether or sulfoxide‐type pleuromutilin derivatives containing heteroaromatic substituents at the end of C14 side chain were designed and synthesized. All of the derivatives were evaluated for their in vitro antibacterial activity. Some of them showed good to excellent antibacterial activity comparable to retapamulin and azamulin in most of the tested Gram‐positive pathogens. In this work, a five‐membered heterocyclic moiety, a pyrimidine‐heterocyclic moiety, or a benzoheterocyclic moiety was introduced in the C14 side chain to increase the structural diversity of the pleuromutilin derivatives. The antibacterial results reveal that the thioether‐containing pleuromutilin derivatives exert a more potency activity than the sulfoxide‐type derivatives against Gram‐positive pathogens. The structure−activity relationship summarized in this work may provide with some interesting clues as to which functionalities are beneficial for high antimicrobial activity of the pleuromutilin derivatives.