Abstract
Nucleoside analogues acyclovir, valaciclovir, and famciclovir are the preferred drugs against human Herpes Simplex Viruses (HSVs). However, the viruses rapidly develop resistance against these analogues which demand safer, more efficient, and nontoxic antiviral agents. We have synthesized two non-nucleoside amide analogues, 2-Oxo-2H-chromene-3-carboxylic acid [2-(pyridin-2-yl methoxy)-phenyl]-amide (HL1) and 2-hydroxy-1-naphthaldehyde-(4-pyridine carboxylic) hydrazone (HL2). The compounds were characterized by different physiochemical methods including elementary analysis, FT-IR, Mass spectra, 1H–NMR; and evaluated for their antiviral efficacy against HSV-1F by Plaque reduction assay. The 50% cytotoxicity (CC50), determined by MTT test, revealed that HL1 (270.4 μg/ml) and HL2 (362.6 μg/ml) are safer, while their antiviral activity (EC50) against HSV-1F was 37.20 μg/ml and 63.4 μg/ml against HL1 and HL2 respectively, compared to the standard antiviral drug Acyclovir (CC50 128.8 ± 3.4; EC50 2.8 ± 0.1). The Selectivity Index (SI) of these two compounds are also promising (4.3 for HL1 and 9.7 for HL2), compared to Acyclovir (49.3). Further study showed that these amide derivatives block the early stage of the HSV-1F life cycle. Additionally, both these amides make the virus inactive, and reduce the number of plaques, when infected Vero cells were exposed to HL1 and HL2 for a short period of time.
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Acknowledgements
ADM received a fellowship from the Department of Science & Technology (DST)-INSPIRE, Government of India; and a project under DC was financially supported by a research grant from the DST, Government of West Bengal [Memo 362 (Sanc.)/ST/P/S&T/9G-32/2014].
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This research uses quality control strain of HSV-1 (ATCC), but no human subjects are involved, and thus there is no need to acquire any ethical approval.
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Das Mahapatra, A., Patra, C., Sepay, N. et al. Anti-HSV nucleoside and non-nucleoside analogues: spectroscopic characterisation of naphthyl and coumarinyl amides and their mode and mechanism of antiviral action. 3 Biotech 13, 245 (2023). https://doi.org/10.1007/s13205-023-03658-0
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DOI: https://doi.org/10.1007/s13205-023-03658-0