Synthesis, Characterization, Toxicity Analysis and in silico Evaluation of New 1,4-Benzopyrone Analogue against Human Metapneumovirus (HMPV) and Respiratory Syncytial Virus (RSV)

Abstract

The global threat posed by recent respiratory viruses necessitates the development of novel antiviral agents. This study focused on the design, synthesis, characterization and cytotoxicity evaluation of two new coumarin analogues, 4-((5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)methoxy)-2H-benzopyrone (4) and N-(4-chloro-benzylidene)-2-((2H-benzopyrone-4-yl)oxy)acetohydrazide (5). These compounds were synthesized from hydrazide derivative of benzopyrone (3) through reactions with 4-hydroxybenzoic acid and 4-chlorobenzaldehyde, respectively. Structural confirmation was achieved using IR, NMR and mass spectrometry. The cytotoxicity was assessed using the MTT assay, demonstrating significant cell viability in HEK-293 cells. Molecular docking studies were performed to evaluate the interaction of the synthesized compounds with RNA-dependent RNA polymerases of human metapneumovirus (HMPV) (PDB ID: 8FPJ) and respiratory syncytial virus (RSV) (PDB ID: 8FPI). Both compounds exhibited high docking scores, indicating strong potential for inhibiting these essential viral enzymes. These findings highlight compounds 4 and 5 as promising candidates for further development as antiviral agents targeting HMPV and RSV. Interestingly, this is the first-time investigation in which benzopyrones have been explored to exhibit significant in silico activity against HMPV. However, future studies should be focused on their preclinical evaluation to establish their therapeutic potential in HMPV treatment.