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Targeting HIV‐TB coinfection by developing novel piperidin‐4‐substituted imines: Design, synthesis, in vitro and in silico studies
Author(s) -
Kumar Avinash,
Revathi Rajappan,
Sriram Dharmarajan,
Curreli Francesca,
Debnath Asim K.,
Pai K. Sreedhara,
Kini Suvarna G.
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800358
Subject(s) - mycobacterium tuberculosis , protein data bank (rcsb pdb) , docking (animal) , in silico , tuberculosis , ethambutol , pharmacology , drug , reverse transcriptase , human immunodeficiency virus (hiv) , in vitro , chemistry , virology , medicine , stereochemistry , biochemistry , rna , nursing , pathology , gene
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 IC 50 of 2.1 ± 0.04 μM in multicycle infection assays, in comparison with the standard drug, zidovudine (IC 50 = 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.