Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines

Rashad Al-Salahi; El Hassane Anouar; Mohamed Marzouk; Hatem A Abuelizz

doi:10.1016/j.bmcl.2019.04.043

Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines

Bioorg Med Chem Lett. 2019 Jul 1;29(13):1614-1619. doi: 10.1016/j.bmcl.2019.04.043. Epub 2019 Apr 27.

Authors

Rashad Al-Salahi¹, El Hassane Anouar², Mohamed Marzouk³, Hatem A Abuelizz⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: ralsalahi@ksu.edu.sa.
² Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia.
³ Chemistry of Natural Products Group, Centre of Excellence for Advanced Sciences, National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.) Dokki, Cairo 12622, Egypt.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.

PMID: 31054861
DOI: 10.1016/j.bmcl.2019.04.043

Abstract

Synthesized 3-benzyl(phenethyl)benzo[g]quinazolines (1-17) were evaluated in vitro to determine their effects against the anti-hepatitis A virus (HAV) using a cytopathic effect inhibition assay. Of the synthesized compounds, 16 and 17 showed considerably high anti-HAV activity, as indicated by their EC₅₀ values of 27.59 and 18 μM, respectively, when compared to that of amantadine (37.3 μM), the standard therapeutic agent. In addition, they exhibited low cytotoxicity as indicated by their CC₅₀ values, 290.63 and 569.45 μM, respectively. Compounds 1, 2, and 5 exhibited remarkable activity compared to the active compounds (16, 17) and amantadine. The selectivity index (SI) values were calculated and applied as a parameter for classifying the activity of the targets. In addition, molecular docking was performed to rationalize the SAR of the target compounds and analyze the binding modes between the docked-selected compounds and amino acid residues in the active site of the HAV-3C proteinase enzyme.

Keywords: 3C proteinase; Antiviral; Benzoquinazolines; Cytopathic effect; Cytotoxicity; Molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use*
Hepatitis A virus / pathogenicity*
Humans
Molecular Docking Simulation
Quinazolines / pharmacology
Quinazolines / therapeutic use*
Structure-Activity Relationship

Substances

Antiviral Agents
Quinazolines