Synthesis, molecular docking screening, ADMET and dynamics studies of synthesized 4-(4-methoxyphenyl)-8-methyl-3,4,5,6,7,8-hexahydroquinazolin-2(1H)-one and quinazolinone derivatives

Abstract For evaluating a synthesis studies, 4-(4-methoxyphenyl)-8-methyl-3, 4, 5, 6, 7, 8- hexahydroquinazolin-2 (1H)-one (QZL7) was synthesized, and the structure was confirmed by spectral characterization techniques FTIR, NMR, and UV spectroscopy, as well as computational data for making comparative study. The density functional theory (DFT) calculations were executed for the QZL7 using B3LYP/6–31++G (d, p) which was also used for the illustration of HOMO and LUMO, vibrational properties and charge distribution potential. The synthesized compound and its probably derivatives were evaluated for their antimicrobial activities along with molecular docking study for five proteins (PDB ID: 6IGF, 1A7G, 6IDB, 6Q0O and 1RXF) by AutoDock. The binding affinity from molecular docking score for QZL1(-6.8 kcal/mol) and QZL4(-6.8 kcal/mol) against the pathogen, E. Coli(6IGF), gives the evidence for being potential antimicrobial agent while the QZL1 (-7.10 kcal/mol) result is also obtained against Streptomyces clavuligerus(1RXF). Molecular dynamics (MD) simulation was performed using YASARA for 10 ns confirming the conformational stability of QZL1+1RXF (protein-ligand) complex. In addition, in-silico ADMET study, bioactivity and toxicity parameters were calculated for quinazolinone and its derivatives (QZL1-7) for evaluating their safe uses and predicting the pre-study of clinical phases as drug molecule by using software and online data base. All the designed molecules passed successfully and utterly Lipinski's rule of five, and they were found to be safe with the calculation as non-carcinogenic with low aquatic and non-aquatic toxicity. Our designed new quinazolinone and quinazoline derivatives might be revealed as first-rate and superior pharmacological profile in medicinal chemistry which may provide the leading information for further studies about their biological activity.