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HTS, Chemical Hybridization, and Drug Design Identify a Chemically Unique Antituberculosis Agent–Coupling Serendipity and Rational Approaches to Drug Discovery
Author(s) -
Mao Jialin,
Wan Baojie,
Wang Yuehong,
Franzblau Scott G.,
Kozikowski Alan P.
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700048
Subject(s) - serendipity , drug , mycobacterium tuberculosis , chemical library , nitrile , drug discovery , tuberculosis , drug candidate , cycloaddition , combinatorial chemistry , chemistry , computational biology , computer science , pharmacology , small molecule , biology , medicine , organic chemistry , physics , biochemistry , pathology , catalysis , astronomy
The high throughput screening of two chemical libraries against Mycobacterium tuberculosis led to the design of hybrid compounds by using nitrile oxide cycloaddition chemistry. One of the hybrids shows an excellent MIC against M. tuberculosis H37Rv. As this molecule shows no CYP3A4 inhibition and a maximum tolerated dose of ≥200 mg kg −1 po in mice, it represents a potential drug candidate for TB therapy.