Targeting HIV-TB coinfection by developing novel piperidin-4-substituted imines

Design, synthesis, in vitro and in silico studies

Avinash Kumar, Rajappan Revathi, Dharmarajan Sriram, Francesca Curreli, Asim K. Debnath, K. Sreedhara Pai, Suvarna G. Kini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1800358
JournalArchiv der Pharmazie
Volume352
Issue number6
DOIs
Publication statusPublished - 01-06-2019

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Imines
Coinfection
Computer Simulation
HIV
Anti-HIV Agents
Inhibitory Concentration 50
Tuberculosis
Pharmaceutical Preparations
Antitubercular Agents
Ethambutol
Zidovudine
RNA-Directed DNA Polymerase
Mycobacterium tuberculosis
Oxidoreductases
In Vitro Techniques
Safety
Infection

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

Kumar, Avinash ; Revathi, Rajappan ; Sriram, Dharmarajan ; Curreli, Francesca ; Debnath, Asim K. ; Pai, K. Sreedhara ; Kini, Suvarna G. / Targeting HIV-TB coinfection by developing novel piperidin-4-substituted imines : Design, synthesis, in vitro and in silico studies. In: Archiv der Pharmazie. 2019 ; Vol. 352, No. 6.
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Targeting HIV-TB coinfection by developing novel piperidin-4-substituted imines : Design, synthesis, in vitro and in silico studies. / Kumar, Avinash; Revathi, Rajappan; Sriram, Dharmarajan; Curreli, Francesca; Debnath, Asim K.; Pai, K. Sreedhara; Kini, Suvarna G.

In: Archiv der Pharmazie, Vol. 352, No. 6, 1800358, 01.06.2019.

Research output: Contribution to journalArticle

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