Open AccessIn Vitro Evaluation of Novel Nitazoxanide Derivatives against Mycobacterium tuberculosis
Author(s) -
Joshua Odingo,
Mai A. Bailey,
Megan Files,
Julie V. Early,
Torey Alling,
Devon Dennison,
Julie Bowman,
Suryakanta Dalai,
Naresh Kumar,
Jeffrey Cramer,
Thierry Masquelin,
Philip A. Hipskind,
Tanya Parish
Publication year - 2017
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.7b00892
Subject(s) - mycobacterium tuberculosis , in vitro , antibacterial activity , microbiology and biotechnology , bacteria , nitazoxanide , tuberculosis , chemistry , pharmacology , biology , biochemistry , medicine , immunology , pathology , genetics
Nitazoxanide has antiparasitic and antibiotic activities including activity against Mycobacterium tuberculosis . We prepared and evaluated a set of its analogues to determine the structure-activity relationship, and identified several amide- and urea-based analogues with low micromolar activity against M. tuberculosis in vitro. Pharmacokinetics in the rat suggested a path forward to obtain bioavailable compounds. The series had a good microbiological profile with bactericidal activity in vitro against replicating and nonreplicating M. tuberculosis . Analogues had limited activity against other Gram-positive bacteria but no activity against Gram-negative bacteria. Our studies identified the key liability in this series as cytotoxicity. Future work concentrating on identifying the target(s) could assist in removing activity against eukaryotic cells.