title: Docking and antiherpetic activity of 2-aminobenzo[de]-isoquinoline-1,3-diones.
abstract: As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50), furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 14‒16 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 μg/mL), compared to acyclovir as a reference drug (EC50 = 1.8 μg/mL). Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo[de]isoquinoline-1,3-dione), while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50), EC50, and the selectivity index (SI) values were determined. In a molecular docking study, the ligand-receptor interactions of compounds 1-24 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD) software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones is warranted.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors: Rashad
authors: R
authors: Al-Salahi
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ialsuwidan@ksu.edu.sa.
authors: Ibrahim
authors: I
authors: Alswaidan
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.
authors: Hazem A
authors: HA
authors: Ghabbour
authors: Drug Bioavailability Lab., College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ezzeldin24@hotmail.com.
authors: Essam
authors: E
authors: Ezzeldin
authors: Regional Center for Mycology and Biotechnology, Al-Azhar University, Naser City, Cairo 11759, Egypt. mmelaasser@hotmail.com.
authors: Mahmoud
authors: M
authors: Elaasser
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. mohmarzouk@ksu.edu.sa.|Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Cairo 12622, Egypt. mohmarzouk@ksu.edu.sa.
authors: Mohamed
authors: M
authors: Marzouk
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D002522:Chlorocebus aethiops; D006801:Humans; D062105:Molecular Docking Simulation; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology; D013937:Thymidine Kinase / Q000737:chemistry; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011804:Quinolines; D013937:Thymidine Kinase