Targeting HIV‐TB coinfection by developing novel piperidin‐4‐substituted imines: Design, synthesis, in vitro and in silico studies

Kumar, Avinash and Revathi, Rajappan and Pai, Sreedhara K and Kini, Suvarna G (2019) Targeting HIV‐TB coinfection by developing novel piperidin‐4‐substituted imines: Design, synthesis, in vitro and in silico studies. Archiv der Pharmazie, 352 (6). pp. 1-12. ISSN 0365-6233

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Abstract

Tuberculosis is the “Achilles heel” of the human immunodeficiency (HIV) ministration.HIV‐positive people are 16–27 times more prone to contract tuberculosis. But the adverse interaction between antiretroviral drugs and antitubercular drugs has made it necessary to look for a single drug regimen for HIV‐TB coinfection. Piperidine derivatives have been reported as anti‐HIV and anti‐TB agents. This inspired us to design, synthesize, and characterize a series of 3,5‐bis furan‐2‐ylmethylidene)‐piperidin‐4‐substituted imines (R1‒R25) and these were further screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv and anti‐HIV activity. Molecular docking studies showed energetically favorable binding interactions with both EACP reductase (1ZID.pdb) and reverse‐transcriptase (1REV.pdb)targets. The compounds R7, R12, R17, R18, R19, R20 were found to be more potent as anti‐TB agents than ethambutol (MIC 3.125 μg/ml). Compound R7 was found to be moderately active with an IC50 of 2.1 ± 0.04 μM in multicycle infection assays, in comparison with the standard drug, zidovudine (IC50 = 5.7 ± 0.04 nM), used as anti‐HIV drug. The cytotoxicity assay was done on Vero, MT‐2, and TZM‐bl cells to assess the safety of these compounds and they were found to be safe. From the above results, R7 seems to be a promising lead for anti‐HIV and anti‐TB activity.

Item Type: Article
Uncontrolled Keywords: Enoyl‐acyl carrier protein reductase; HIV; Mycobacterium tuberculosis; piperidine; Reverse‐transcriptase
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 13 Sep 2019 05:50
Last Modified: 13 Sep 2019 05:52
URI: http://eprints.manipal.edu/id/eprint/154506

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