A nano-mgo and ionic liquid-catalyzed `green' synthesis protocol for the development of adamantyl-imidazolo-thiadiazoles as anti-tuberculosis agents targeting sterol 14 alpha-demethylase (cyp51)

Anusha, S. and Baburajeev, C. P. and Mohan, C. D. and Mathai, J. and Rangappa, S. and Mohan, S. and Chandra and Paricharak, S. and Mervin, L. and Fuchs, J. E. and Mahedra, M. and Bender, A. and Basappa and Rangappa, K. S. (2015) A nano-mgo and ionic liquid-catalyzed `green' synthesis protocol for the development of adamantyl-imidazolo-thiadiazoles as anti-tuberculosis agents targeting sterol 14 alpha-demethylase (cyp51). PLOS ONE, 10 (10). ISSN 1932-6203

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Official URL: http://doi.org/10.1371/journal.pone.0139798

Abstract

In this work, we describe the `green' synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo 2,1-b]1,3,4] thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)- 2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H(37)Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl) imidazo2,1-b]1,3,4] thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 mu M. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14 alpha-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity.

Item Type: Article
Subjects: C Chemical Science > Chemistry
D Physical Science > Physics
Divisions: Department of > Chemistry
Department of > Physics
Depositing User: Shrirekha lpasrirekha user
Date Deposited: 30 May 2019 07:01
Last Modified: 30 May 2019 07:01
URI: http://eprints.uni-mysore.ac.in/id/eprint/669

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