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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
2-Aryl benzazole derived new class of anti-tubercular compounds: Endowed to eradicate mycobacterium tuberculosis in
Anand Babu Velappan1, Dhrubajyoti Datta2, Rui Ma3
1Department of Chemistry, SCBT, SASTRA Deemed to be University, Tamilnadu 613401, India.
Abstract:
The high mortality rate and the increasing prevalence of Mtb resistance are the major concerns for the Tuberculosis (TB) treatment in this century. To counteract the prevalence of Mtb resistance, we have synthesized 2-aryl benzazole based dual targeted molecules. Compound 9m and 9n were found to be equally active against replicating and non-replicating form of Mtb (MIC(MABA) 1.98 and 1.66 μg/ml; MIC(LORA) 2.06 and 1.59 μg/ml respectively). They arrested the cell division (replicating Mtb) by inhibiting the GTPase activity of FtsZ with IC50 values 45 and 64 μM respectively. They were also capable of kill Mtb in non-replicating form by inhibiting the biosynthesis of menaquinone which was substantiated by the MenG inhibition (IC50 = 11.62 and 7.49 μM respectively) followed by the Vit-K2 rescue study and ATP production assay.
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