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

Publication date: Available online 27 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Rudraraju Srilakshmi Reshma, Variam Ullas Jeankumar, Nidhi Kapoor, Shalini Saxena, Karyakulam Andrews Bobesh, Astakala Rishi Vachaspathy, Pappachan E Kolattukudy, Dharmarajan Sriram
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 benzthiazole 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 ± 1.21 µM). Compound 22 exhibits bactericidal action against nutrient starved Mycobacterium tuberculosis (MTB). It also exhibits significant activity in nutrient starvation model (2.9 log folds) and biofilm model (2.3 log folds).

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