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Tuberculosis Research and Treatment
Volume 2012 (2012), Article ID 289136, 7 pages
http://dx.doi.org/10.1155/2012/289136
Research Article

Antimycobacterial Activities of Novel 5-(1H-1,2,3-Triazolyl)Methyl Oxazolidinones

1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait
2Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait

Received 17 November 2011; Accepted 14 February 2012

Academic Editor: Zarir Farokh Udwadia

Copyright © 2012 Oludotun Adebayo Phillips et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The antibacterial activities of a series of triazolyl oxazolidinones against Mycobacterium tuberculosis strain in vitro and in vivo in a mice model are presented. Most active compounds were noncytotoxic against VERO cells with acceptable selectivity indexes (SI) as measures of compound tolerability. Structure activity relationships (SARs) revealed that analogs with alkylcarbonyl (IC90: < 0.2 to 0.422 μg/mL) and arylcarbonyl (IC90: < 0.2 to 2.103 μg/mL) groups at the piperazine 4N-position-displayed potent antimycobacterium activities, comparable to the methanesulfonyl (IC90: < 0.2 μg/mL) analog, linezolid (IC90: < 0.2 μg/mL), and isoniazid (IC90: < 0.034 μg/mL). The furanylcarbonyl derivative also displayed potent activity, while the arylsulfonyl analogs were inactive. Of the triazolyl oxazolidinones, the morpholino (PH-27) derivative with medium bioavailability in plasma was most active in vivo, but relatively less efficacious than isoniazid.