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

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.
Rashad Al-Salahi 1,  El Hassane Anouar 2,  Mohamed Marzouk 3,  Hatem A Abuelizz 4
Affiliations

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.

Figures