1. 2-Aryl benzazole derived new class of anti-tubercular compounds: Endowed to eradicate mycobacterium tuberculosis in replicating and non-replicating forms
- Author
-
Anand Babu Velappan, Scott G. Franzblau, Natarajan Hari, Rui Ma, Joy Debnath, Dhrubajyoti Datta, Shiwani Rana, and Kalyan Sundar Ghosh
- Subjects
Tuberculosis ,Cell division ,Antitubercular Agents ,01 natural sciences ,Biochemistry ,Microbiology ,Mycobacterium tuberculosis ,chemistry.chemical_compound ,Biosynthesis ,Drug Discovery ,Ic50 values ,medicine ,Humans ,FtsZ ,Anti tubercular ,Molecular Biology ,biology ,010405 organic chemistry ,Aryl ,Organic Chemistry ,medicine.disease ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,biology.protein - 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.
- Published
- 2020