@article { ISI:000306324500011,
	title = {Potential use of nitrate reductase as a biomarker for the identification of active and dormant inhibitors of mycobacterium tuberculosis in a THP1 infection model},
	journal = {Journal of Biomolecular Screening},
	volume = {17},
	number = {7},
	year = {2012},
	month = {AUG},
	pages = {966-973},
	publisher = {SAGE PUBLICATIONS INC},
	address = {2455 TELLER RD, THOUSAND OAKS, CA 91320 USA},
	abstract = {<p>The development of a macrophage-based, antitubercular high-throughput screening system could expedite discovery programs for identifying novel inhibitors. In this study, the kinetics of nitrate reduction (NR) by Mycobacterium tuberculosis during growth in Thp1 macrophages was found to be almost parallel to viable bacilli count. NR in the culture medium containing 50 mM of nitrate was found to be optimum on the fifth day after infection with M. tuberculosis. The signal-to-noise (S/N) ratio and Z-factor obtained from this macrophage-based assay were 5.4 and 0.965, respectively, which confirms the robustness of the assay protocol. The protocol was further validated by using standard antitubercular inhibitors such as rifampicin, isoniazid, streptomycin, ethambutol, and pyrazinamide, added at their IC90 value, on the day of infection. These inhibitors were not able to kill the bacilli when added to the culture on the fifth day after infection. Interestingly, pentachlorophenol and rifampicin killed the bacilli immediately after addition on the fifth day of infection. Altogether, this assay protocol using M. tuberculosis-infected Thp-1 macrophages provides a novel, cost-efficient, robust, and easy-to-perform screening platform for the identification of both active and hypoxic stage-specific inhibitors against tuberculosis.</p>},
	keywords = {high-throughput screening, inhibitor, Mycobacterium tuberculosis, nitrate reductase, THP1},
	issn = {1087-0571},
	doi = {10.1177/1087057112445485},
	author = {Sarkar, Sampa and Sarkar, Dhiman}
}
@article {48349,
	title = {Detection of a target protein (GroEl2) in Mycobacterium tuberculosis using a derivative of 1,2,4-triazolethiols},
	journal = {Molecular Diversity},
	volume = {26},
	year = {2022},
	month = {OCT},
	pages = {2535-2548},
	type = {Article},
	abstract = {<p>
	Herein, we identified a potent lead compound RRA2, within a series of 54 derivatives of 1,2,4-triazolethiols (exhibit good potency as an anti-mycobacterial agents) against intracellular Mycobacterium tuberculosis (Mtb). Compound RRA2 showed significant mycobactericidal activity against active stage Mycobacterium bovis BCG and Mtb with minimum inhibitory concentration (MIC) values of 2.3 and 2.0 mu g/mL, respectively. At MIC value, RRA2 compound yielded 0.82 log reduction of colony-forming unit (cfu) against non-replicating Mtb. Furthermore, RRA2 compound was selected for further target identification due to the presence of alkyne group, showing higher selectivity index (\&gt; 66.66 +/- 0.22, in non-replicating stage). Using {\textquoteleft}{\textquoteleft}click{\textquoteright}{\textquoteright} chemistry, we synthesized the biotin linker-RRA2 conjugate, purified with HPLC method and confirmed the conjugation of biotin linker-RRA2 complex by HR-MS analysis. Furthermore, we successfully pulled down and identified a specific target protein GroEl2, from Mtb whole-cell extract. Furthermore, computational molecular modeling indicated RRA2 could interact with GroEl2, which explains the structure-activity relationship observed in this study.</p>
},
	keywords = {1, 2, 4-triazolethiols, GroEl2, Mycobactericidal activity, Mycobacterium bovis BCG, Mycobacterium tuberculosis},
	issn = {1381-1991},
	doi = {10.1007/s11030-021-10351-y},
	author = {Sarkar, Sampa and Swami, Sagar and Soni, Sarvesh Kumar and Holien, Jessica K. and Khan, Arshad and Korwar, Arvind M. and Likhite, Anjali P. and Joshi, Ramesh A. and Joshi, Rohini R. and Sarkar, Dhiman}
}
