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Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound

Twelve N-substituted-glycinyl triazolyl oxazolidinone derivatives were screened for antimycobacterial activity against susceptible (Mycobacterium tuberculosis (Mtb) H37Rv) and resistant (isoniazid (INH)-resistant Mtb (SRI 1369), rifampin (RMP)-resistant Mtb (SRI 1367), and ofloxacin (OFX)-resistant...

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Autores principales: Al-Tannak, Naser F., Phillips, Oludotun A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748531/
https://www.ncbi.nlm.nih.gov/pubmed/28974052
http://dx.doi.org/10.3390/scipharm85040034
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author Al-Tannak, Naser F.
Phillips, Oludotun A.
author_facet Al-Tannak, Naser F.
Phillips, Oludotun A.
author_sort Al-Tannak, Naser F.
collection PubMed
description Twelve N-substituted-glycinyl triazolyl oxazolidinone derivatives were screened for antimycobacterial activity against susceptible (Mycobacterium tuberculosis (Mtb) H37Rv) and resistant (isoniazid (INH)-resistant Mtb (SRI 1369), rifampin (RMP)-resistant Mtb (SRI 1367), and ofloxacin (OFX)-resistant Mtb (SRI 4000)) Mtb strains. Most of the compounds showed moderate to strong antimycobacterial activity against all strains tested, with minimum inhibitory concentration (MIC) value ranges of 0.5–11.5, 0.056–11.6, 0.11–5.8, and 0.03–11.6 μM, and percent inhibition ranges of 41–79%, 51–72%, 50–75%, and 52–71% against Mtb H37Rv, INH-R, RMP-R, and OFX-R M. tuberculosis, respectively. The 3,5-dinitrobenzoyl and 5-nitrofuroyl derivatives demonstrated strong antimycobacterial activities with the N-(5-nitrofuroyl) derivatives (PH-145 and PH-189) being the most potent, with MIC value range of 0.3–0.6 μM against all strains tested. Compounds were not bactericidal, but showed intracellular (macrophage) antimycobacterial activity. A reliable validated analytical method was developed for a representative compound PH-189 using Waters Acquity ultra High-Performance Liquid Chromatography (UHPLC) system with quaternary Solvent Manager (H-Class). A simple extraction method indicated that PH-189 was stable in human plasma after 90 min at 37 °C with more than 90% successfully recovered. Moreover, stress stability studies were performed and degradants were identified by using UHPLC-ESI-QToF under acidic, basic, and oxidative simulated conditions.
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spelling pubmed-57485312018-01-12 Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound Al-Tannak, Naser F. Phillips, Oludotun A. Sci Pharm Article Twelve N-substituted-glycinyl triazolyl oxazolidinone derivatives were screened for antimycobacterial activity against susceptible (Mycobacterium tuberculosis (Mtb) H37Rv) and resistant (isoniazid (INH)-resistant Mtb (SRI 1369), rifampin (RMP)-resistant Mtb (SRI 1367), and ofloxacin (OFX)-resistant Mtb (SRI 4000)) Mtb strains. Most of the compounds showed moderate to strong antimycobacterial activity against all strains tested, with minimum inhibitory concentration (MIC) value ranges of 0.5–11.5, 0.056–11.6, 0.11–5.8, and 0.03–11.6 μM, and percent inhibition ranges of 41–79%, 51–72%, 50–75%, and 52–71% against Mtb H37Rv, INH-R, RMP-R, and OFX-R M. tuberculosis, respectively. The 3,5-dinitrobenzoyl and 5-nitrofuroyl derivatives demonstrated strong antimycobacterial activities with the N-(5-nitrofuroyl) derivatives (PH-145 and PH-189) being the most potent, with MIC value range of 0.3–0.6 μM against all strains tested. Compounds were not bactericidal, but showed intracellular (macrophage) antimycobacterial activity. A reliable validated analytical method was developed for a representative compound PH-189 using Waters Acquity ultra High-Performance Liquid Chromatography (UHPLC) system with quaternary Solvent Manager (H-Class). A simple extraction method indicated that PH-189 was stable in human plasma after 90 min at 37 °C with more than 90% successfully recovered. Moreover, stress stability studies were performed and degradants were identified by using UHPLC-ESI-QToF under acidic, basic, and oxidative simulated conditions. MDPI 2017-10-02 2017 /pmc/articles/PMC5748531/ /pubmed/28974052 http://dx.doi.org/10.3390/scipharm85040034 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al-Tannak, Naser F.
Phillips, Oludotun A.
Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title_full Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title_fullStr Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title_full_unstemmed Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title_short Antimycobacterial Activities of N-Substituted-Glycinyl 1H-1,2,3-Triazolyl Oxazolidinones and Analytical Method Development and Validation for a Representative Compound
title_sort antimycobacterial activities of n-substituted-glycinyl 1h-1,2,3-triazolyl oxazolidinones and analytical method development and validation for a representative compound
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748531/
https://www.ncbi.nlm.nih.gov/pubmed/28974052
http://dx.doi.org/10.3390/scipharm85040034
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