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- Title
Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds endowed with high activity toward multidrug-resistant Mycobacterium tuberculosis.
- Authors
Dharmarajan Sriram; Perumal Yogeeswari; Murugesan Dinakaran; Rathinasababathy Thirumurugan
- Abstract
: Objectives The objective of this work was to synthesize 15 new 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds and evaluate their in vitro and in vivo antimycobacterial activities. : Methods 5-Cyclobutyloxazol-2-amine was reacted with 1,1′-thiocarbonyldiimidazole, followed by various substituted anilines and 2-amino pyridines to yield the 15 compounds, which were subjected to in vitro and in vivo evaluation against Mycobacterium tuberculosis H37Rv (MTB) and a clinical isolate of multidrug-resistant M. tuberculosis (MDR-TB). : Results Among the 15 compounds screened, 7 compounds inhibited both MTB and MDR-TB in vitro with MICs of < 1 µM. In the in vivo screening, compound 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(2′-trifluoromethyl)phenylthiourea (compound 8) was equally active as isoniazid at the same dose level. : Conclusions Compound 8 was found to be the most active, with an in vitro MIC of 0.14 µM and was 2.5 and 80 times more active than isoniazid against MTB and MDR-TB, respectively. Compound 8 was non-toxic to Vero cells up to 183 µM, with a selectivity index of > 1307. In the in vivo animal model, compound 8 decreased the mycobacterium load in lung and spleen tissues with 2.8 and 3.94 log10 reductions, respectively.
- Subjects
MYCOBACTERIAL diseases; TUBERCULOSIS; MYCOBACTERIUM tuberculosis; MYCOBACTERIUM
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2007, Vol 59, Issue 6, p1194
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkm085