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Design, Synthesis, and Biological Evaluation of Novel Benzoyl Diarylamine/ether Derivatives as Potential Anti‐HIV‐1 Agents
Author(s) -
Zhang Lingzi,
Guo Jian,
Liu Xin,
Liu Huiqing,
De Clercq Erik,
Pannecouque Christophe,
Liu Xinyong
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12497
Subject(s) - chemistry , lead compound , ether , human immunodeficiency virus (hiv) , enzyme , combinatorial chemistry , active compound , stereochemistry , diphenyl ether , rational design , reverse transcriptase , ec50 , in vitro , biochemistry , virology , organic chemistry , biology , rna , genetics , gene
A series of benzoyl diarylamine/ether derivatives were designed, synthesized, and evaluated for their activity against human immunodeficiency virus ( HIV ) in MT ‐4 cells. Three compounds ( 3b , 5a, and 6a1 ) exhibited moderate activities against wild‐type (wt) HIV ‐1 with EC 50 values ranging from 11 to 56 μ m . Among them, compound 5a was the most potent inhibitor with a novel chemical skeleton, affording a new lead compound for further molecular optimization. An enzyme assay was also implemented to confirm the binding target of the active compounds represented by 6a1 . Molecular simulation studies on compound 5a , 6a1, and 7a4 were carried out to understand their binding mode with wt HIV ‐1 reverse transcriptase ( RT ) and provided useful information for further rational design of NNRTI s.