Design, synthesis, and anti-HIV-1 activity of 1-substituted 3-(3,5-dimethylbenzyl)triazine derivatives

Background: Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. Objective: Novel series of thioimidazolyl diketo acid derivatives characterizing various substituents at N-1 and 2-thio positions of central ring were developed as HIV-1 integrase inhibitors. Results: The obtained molecules were evaluated in the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 M. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. Conclusion: The most potent compound was 18i with EC50=19 µM, IC50 0.9 µM and SI= 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1 integrase inhibitors.

Download Full-text

Design, Synthesis and Docking Studies of New 4-hydroxyquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 Agents

Drug Research ◽

10.1055/s-0033-1334964 ◽

2013 ◽

Vol 63 (04) ◽

pp. 192-197 ◽

Cited By ~ 6

Author(s):

Z. Hajimahdi ◽

R. Zabihollahi ◽

M. Aghasadeghi ◽

A. Zarghi

Keyword(s):

Docking Studies ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

Download Full-text

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives

Antiviral Chemistry and Chemotherapy ◽

10.1177/2040206614566584 ◽

2015 ◽

Vol 24 (1) ◽

pp. 3-18 ◽

Cited By ~ 5

Author(s):

Norikazu Sakakibara ◽

Masanori Baba ◽

Mika Okamoto ◽

Masaaki Toyama ◽

Yosuke Demizu ◽

...

Keyword(s):

Urea Derivatives ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1 ◽

Substituted Urea

Download Full-text

Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives as potent HIV-1 NNRTIs

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2017.07.012 ◽

2017 ◽

Vol 140 ◽

pp. 383-391 ◽

Cited By ~ 11

Author(s):

Zhaoqiang Liu ◽

Ye Tian ◽

Jinghan Liu ◽

Boshi Huang ◽

Dongwei Kang ◽

...

Keyword(s):

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

Download Full-text

Rational design, synthesis, anti-HIV-1 RT and antimicrobial activity of novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one derivatives

Bioorganic Chemistry ◽

10.1016/j.bioorg.2016.05.009 ◽

2016 ◽

Vol 67 ◽

pp. 75-83 ◽

Cited By ~ 14

Author(s):

Subhash Chander ◽

Ping Wang ◽

Penta Ashok ◽

Liu-Meng Yang ◽

Yong-Tang Zheng ◽

...

Keyword(s):

Antimicrobial Activity ◽

Rational Design ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

Download Full-text

Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay

Medicinal Chemistry ◽

10.2174/1573406415666190826161123 ◽

2020 ◽

Vol 16 (7) ◽

pp. 938-946 ◽

Cited By ~ 1

Author(s):

Mahdieh Safakish ◽

Zahra Hajimahdi ◽

Rouhollah Vahabpour ◽

Rezvan Zabihollahi ◽

Afshin Zarghi

Keyword(s):

Molecular Modeling ◽

Drug Target ◽

Design Synthesis ◽

Metal Chelating ◽

Hydrophobic Site ◽

Π Stacking Interaction ◽

Molecular Modeling Studies ◽

Inhibitory Potential ◽

Anti Hiv ◽

Hiv 1

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3’-end nucleotide as a streamlined metal chelating pharmacophore. Method: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone. Results: Molecular modeling studies revealed that amide functionality alongside oxadiazole heteroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupies hydrophobic site created by the cytidylate nucleotide (DC-16). Conclusion: The most potent and selective compound displayed 110 μM IC50 with a selectivity index of more than 2.

Download Full-text