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Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 4-[4-Arylpyridin-1(4H)-Yl]Benzoic Acid Derivatives As Anti-Hiv-1 Agents Publisher Pubmed



Sepehri S1, 2 ; Soleymani S3 ; Zabihollahi R3 ; Aghasadeghi MR3 ; Sadat M3 ; Saghaie L1 ; Fassihi A1
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, 56189-53141, Iran
  3. 3. Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, 13169-43551, Iran

Source: Chemistry and Biodiversity Published:2017


Abstract

The structural similarities between N1 substituted 1,4-dihydropyridines and the known gp41 inhibitors, NB-2 and NB-64, were considered in the current research for the design of some novel anti-HIV-1 agents. A series of novel 4-[4-arylpyridin-1(4H)-yl]benzoic acid derivatives were synthesized and after a comprehensive structural elucidation were screened for in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate to good inhibitory activity against HIV-1 growth and were evaluated for in vitro cytotoxic activity using XTT assay at the concentration of 100 μm. Among the tested compounds, 1c, 1d and 1e showed potent anti-HIV-1 activity against P24 expression at 100 μm with inhibition percentage of 84.00%, 76.42% and 80.50%, respectively. All the studied compounds possessed no significant cytotoxicity on MT-2 cell line. The binding modes of these compounds to gp41 binding site were determined through molecular docking study. Docking studies proved 1a as the most potent compound and binding maps exhibited that the activities might be attributed to the electrostatic and hydrophobic interactions and additional H-bonds with the gp41 binding site. The Lipinski's ‘rule of five’ and drug-likeness criteria were also calculated for the studied compounds. All derivatives obeyed the Lipinski's ‘rule of five’ and had drug-like features. The findings of this study suggest that novel 4-[4-arylpyridin-1(4H)-yl]benzoic acid might be a promising scaffold for the discovery and development of novel anti-HIV-1 agents. © 2017 Wiley-VHCA AG, Zurich, Switzerland
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