Design, synthesis, molecular docking, biological evaluation, DFT and ADME studies of novel bisquinazolinone derivatives

Abstract

Novel derivatives of bisquinazolinones and bisfuramides were synthesized and tested for their efficiency in this work. Within short reaction times (1–10 min), bisfuramide derivatives were synthesized through the interaction of the ring opening of bis benzoxazin-4-one with primary aromatic amines. FT-IR, 1H NMR, 13C NMR, MS spectral data were used to characterize the structures of newly synthesized compounds. These compounds were screened in vitro antimicrobial activity. The inhibition zone of the synthesized compounds against various bacteria (S. aureus, E. coli) and fungus (C. albicans) was measured by using well and disc diffusion assay. The novel bisquinazolinones were screened for their anti-cancer activity against MCF-7 cell lines, the obtained results clearly reveal moderate to excellent anti-proliferative activity, anti-oxidant activity was performed by using DPPH method. Furthermore, molecular docking analysis revealed a favorable binding contact with the Kinase inhibitor (PDB ID: 1XKK). DFT calculations with B3LYP/6–31 + G (d) level were used to analyze the electronic and geometric characteristics deduced from the stable structure of the compounds. The electron affinity (EA), ionization potential (IP), energy gap (Egap), electronegativity (χ), electrophilicity (ω), hardness (η), softness (S) and electrophilicity index (ωi) were computed and discussed. Furthermore, in silico ADMET (i.e. Absorption, distribution, metabolism, and excretion) calculations were performed on all synthesized compounds that showed potency in comparison to conventional azithromycin.