Mycobacterium tuberculosis lysine-ɛ-aminotransferase a potential target in dormancy: Benzothiazole based inhibitors

Rudraraju Srilakshmi Reshma¹, Variam Ullas Jeankumar¹, Nidhi Kapoor²

¹Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, India.

|April 9, 2017

Abstract:

MTB lysine-ɛ-aminotransferase (LAT) was found to play a crucial role in persistence and antibiotic tolerance. LAT serves as a potential target in the management of latent tuberculosis. In present work we attempted to derivatize the benzothiazole lead identified through high throughput virtual screening of Birla Institute of Technology and Science in house database. For Structure activity relationship purpose 22 derivatives were synthesized and characterized. Among synthesized compounds, eight compounds were found to be more efficacious in terms of LAT inhibition when compared to lead compound (IC₅₀ 10.38±1.21µM). Compound 22 exhibits bactericidal action against nutrient starved Mycobacterium tuberculosis (MTB). It also exhibits significant activity in nutrient starvation model (2.9log folds) and biofilm model (2.3log folds).

Keywords:

3D granuloma model Benzothiazole derivatives Dormancy Lysine-ɛ amino transferase Mycobacterium tuberculosis

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Abstract:

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