Synthesis of various 3-nitropropionamides as Mycobacterium tuberculosis isocitrate lyase inhibitor |
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| Authors: | Sriram Dharmarajan Yogeeswari Perumal Methuku Swetha Vyas Devambatla Ravi Kumar Senthilkumar Palaniappan Alvala Mallika Jeankumar Variam Ullas |
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| Institution: | Antitubercular Drug Discovery Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India. dsriram@bits-hyderabad.ac.in |
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| Abstract: | Various 3-nitropropionamides were synthesized and evaluated for in vitro activities against log and starved phase culture of two mycobacterial species and Mycobacterium tuberculosis (MTB) isocitrate lyase (ICL) enzyme inhibition studies. Among 22 compounds, 1-cyclopropyl-7-(3,5-dimethyl-4-(3-nitropropanoyl)piperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (22) was found to be the most active compound in vitro with MICs of 0.16 and 0.04 μM against log- and starved-phase culture of MTB. Compound 22 also showed good enzyme inhibition of MTB ICL with IC(50) of 0.10 ± 0.01 μM. The docking studies also confirmed the binding potential of the compounds at the ICL active site. |
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| Keywords: | Antitubercular activity Mycobacterium tuberculosis Nitropropionic acid derivatives Latent tuberculosis |
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