Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives.
BACKGROUND
The persistent appearance of viral strains that causes a resistant viral infection has led to continuous trials for the design and development of novel antiviral compounds. Benzoquinazoline compounds have been reported to exhibit an interesting antiviral activity. This work aims to study and evaluate the antiviral activity of a newly prepared 2-thioxo-benzo[g]quinazolin-4(3H)-one series against herpes simplex (HSV-1 & 2) and coxsackievirus (CVB4).


METHODS
The antiviral activity was performed using the MTT assay, in which Vero cells (obtained from the American Type Culture Collection, ATCC) were propagated in fresh Dulbecco's Modified Eagle's Medium (DMEM) and challenged with 10(4) doses of the virus. Thereafter, the cultures were treated simultaneously with two-fold serial dilutions of the tested compound and incubated at 37 °C for 48 h. Molecular docking studies were done on the CVB4 2A proteinase enzyme using Molegro Virtual Docker software.


RESULTS
The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined. Based on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative to their parents. Accordingly, compounds 5-9, 11, 15-18, 21, 22, 24, 25, 27 and 28 were active against CVB4, and compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used as reference drugs.


CONCLUSIONS
The obtained results gave us some useful insights about the characteristic requirements for future trials to build up and design more active and selective antiviral 2-thioxo-benzo[g]quinazolin-4(3H)-one agents.Graphical abstractCompound 24 superimposed with Ribavirin in CV B4 2A Proteinase enzyme (PDB: 1Z8R) active site.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia.
Rashad
R
Al-Salahi
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia.
Hatem A
HA
Abuelizz
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia.
Hazem A
HA
Ghabbour
Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh, 11495 Saudi Arabia ; Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Cairo, 11795 Egypt.
Rabab
R
El-Dib
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451 Saudi Arabia ; Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Cairo, 12622 Egypt.
Mohamed
M
Marzouk
2-Thioxo-benzo[g]quinazolines; Coxsackievirus; HSV; Molecular docking; Ribavirin