A comprehensive investigation of ethyl 2-(3-methoxybenzyl) acrylate substituted pyrazolone analogue: Synthesis, computational and biological studies

Abstract

In this study, we successfully synthesized ethyl 2-(3-methoxybenzyl) acrylate-substituted pyrazolones derivative (EMH) through the reaction of Baylis-Hillman acetate with pyrazolones. We conducted comprehensive screenings to evaluate its invitro antifungal, antibacterial, and antioxidant properties. The molecule demonstrated notable in vitro antifungal and antibacterial activities attributed to the presence of anisole, enhancing absorption rates through increased lipid solubility and improving pharmacological effects. Structure-activity relationship (SAR) studies supported these findings. Additionally, insilico studies delved into the molecular interactions of the synthesized molecule with DNA Gyrase, Lanosterol 14 alpha demethylase, and KEAP1-NRF2 proteins, revealing strong binding interactions at specific sites. Furthermore, we employed ab-initio techniques to theoretically estimate the photophysical properties of the compounds. Ground state optimization, dipole moment, and HOMO-LUMO energy levels were calculated using the DFT-B3LYP-6-31G(d) basis set. The theoretical HOMO-LUMO values indicated high electronegativity and electrophilicity index. NBO analysis confirmed the presence of intermolecular ON...H hydrogen bonds resulting from the interaction of the lone pair of oxygen with the anti-bonding orbital. Overall, our results suggest that anisole-substituted pyrazolones derivatives exhibit promising applications in both photophysical and biological domains.

Keywords

• Pyrazolones
• In-vitro and in-silico biological activity
• HOMO-LUMO
• NBO
• MESP