Synthesis, in-vitro and molecular docking studies of 3,4- dihydropyrmidine-2-(1H) one-based Calix[4]arenes as antimicrobial agent and kinase inhibitor

Abstract

Calix[n]arenes, nowadays, are used as a fully developed synthetic scaffold that provides a variety of spatial arrangement in structural groups which makes them more sufficient to use as a bed to be linked to other important derivatives like dihydropyrimidinone compounds. Recently, great interest has been attracted towards in the development and recognition of dihydropyrimidine derivatives based on calixarene compounds. In this study, A series of derivatives consisting of tetra‑tert-butylcalix[4]arene attached to 3,4-dihydropyrimidine-2-(1H)-one at the lower rim were successfully synthesized. This was achieved through the reaction between 6-bromomethyl-DHPMs compounds (5a-d) and tetra‑tert‑butyl calix[4]arene. The synthesized compounds showed antibacterial and antifungal activities. Compound e exhibited the strongest antibacterial effects among these compounds. The results regarding the antifungal activity suggest that the synthesized compounds, particularly compound c, have significant effectiveness in eradicating fungal pathogens in humans and showed promising performance in this study. Additionally, a molecular docking study of these compounds was conducted, revealing that the novel derivatives d and e act as highly potent inhibitors of EGFR mutants with a unique chemical structure.The synthesized compounds were subjected to characterization using various techniques, including FT-IR spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy, and elemental analysis. These analyses provided spectral data and elemental composition information, allowing for a comprehensive characterization of the synthesized compounds (7a-d).