Open AccessDesign and Syntheses of Anti-Tuberculosis Agents Inspired by BTZ043 Using a Scaffold Simplification Strategy
Author(s) -
Rohit Tiwari,
Ute Möllmann,
Sang Hyun Cho,
Scott G. Franzblau,
Patricia A. Miller,
Marvin J. Miller
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml500039g
Subject(s) - mycobacterium tuberculosis , sulfonamide , amide , ring (chemistry) , tuberculosis , combinatorial chemistry , chemistry , in vitro , in vivo , nitro , scaffold , ex vivo , stereochemistry , biochemistry , medicine , organic chemistry , biology , microbiology and biotechnology , biomedical engineering , alkyl , pathology
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is a global public health concern because of the emergence of various resistant strains. Benzothiazin-4-ones (BTZs), represented by BTZ043, are a promising new class of agents for the treatment of tuberculosis and have been shown to kill Mtb in vitro, ex vivo, and in mouse models of TB. Herein we report the design and syntheses of nitroaromatic sulfonamide, reverse-amide, and ester classes of anti-TB agents using a scaffold simplification strategy based on BTZ043. The presented work explores the effect of functional groups such as sulfonamides, reverse-amides, and esters that are attached to the nitroaromatic rings on their anti-TB activity. The in vitro activity of the compounds evaluated against the H37Rv strain of Mtb show that nitroaromatic sulfonamides and nitrobenzoic acid esters with two nitro substituents were most active and highlights the importance of the electronic character (electron deficient aromatic ring) of the nitroaromatic ring as a central theme in these types of nitroaromatic anti-TB agents.