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 OPEN ACCESSMolecules 2015, 20 5100 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.

Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives

“…We previously reported our findings regarding the antiviral activity of isoquinazoline and triazoloquinazoline derivatives. The results suggested that quinazolines can be good platform for designing a new antiviral agent [ 11 – 13 ]. Here, we are reporting the results of an antiviral investigation for a new series of 2-thioxo-benzo[ g ]quinazolines 1 – 28 (Table 1 and Scheme 1 ) [ 18 ].…”

“…The source and methodology for preparation of the Vero cells were reported in details by Al-Salahi et collaborators [ 11 ]. The GHSV-UL46, G and E2 viral strains were used for the assay of HSV-1, HSV-2 and CVB4 viruses, respectively.…”

“…Screening of the antiviral was performed using MTT assay. According to the literature [ 11 , 22 , 23 ], the Vero cells were cultured, then treated with two-fold serial dilutions of the tested compounds, starting from 1000 μg/mL and diluting to about 2 μg/mL (1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.81, 3.91, 1.95 μg/mL). Six wells were used for each concentration of the tested compound and three independent experiments were assessed, each containing four replicates per treatment [ 24 ].…”

“…Recently, we have reported the biological activity of some prepared triazoloquinazolines against herpes simplex (HSV-1 & 2) and CVB4. However, a number of these prepared compounds were found to possess remarkable and significant antiviral activity [ 11 – 13 ]. Furthermore, synthetic chemistry has shown that benzoquinazoline is a valuable precursor for elaborating many structurally diverse bioactive molecules, particularly as influenza H5N1 and H1N1 antiviral agents [ 14 – 17 ].…”

“…Furthermore, synthetic chemistry has shown that benzoquinazoline is a valuable precursor for elaborating many structurally diverse bioactive molecules, particularly as influenza H5N1 and H1N1 antiviral agents [ 14 – 17 ]. In addition, some 2-aminobenzo[ de ]-isoquinoline-1,3-diones have been reported as antiherpetic agents [ 11 ].…”