Novel indole derivatives of dihydropyrimidinone: Synthesis, characterization, molecular docking and antimicrobial activity

Abstract

The enaminone was reacted with substituted aldehyde and urea in glacial acetic acid. The indole derivatives of dihydropyrimidinone were obtained in good yield. Spectroscopic methods were employed to confirm and characterize the structures of all novel synthesized compounds. All the compounds were screened for antimicrobial activity against Gram-positive, Gram-negative, and Candida albicans. Most of the synthesized compounds were active against all tested trains. Enaminone was found to be highly active against all strains except P. aeruginosa and S. typhi. Enaminone presented (MIC = 64 µg/mL) against S. pneumonia, (MIC = 16 µg/mL) against B. anthracis, and (MIC = 32 µg/mL) against S. aureus as compared to positive control erythromycin (MIC = 8 µg/mL), gentamycin (MIC = 2 µg/mL) and ciprofloxacin (MIC = 4 g/L) respectively. A molecular docking study was performed at the active site of E. coli DNA gyrase, K. pneumonia DNA gyrase, and topoisomerase IV. The results showed that the compound with phenyl substitution exhibited an inhibition zone of 18 mm against E. coli and presented the highest binding energy S = -9.83 kcal/mol. It showed three π−bonds with (DA20, and DT15), aromatic rings in the molecule, and the carboxyl groups of the urea ring chelated Mg2+. Compound with 4-nitrophenyl exhibited an inhibition zone of 13.6 mm against K. pneumoniae. It also presented the highest binding energy S = -9.55 kcal/mol. LYS444 and DC315 were predicted to form an H-bond donor with hydrogen in phenyl and urea rings. All the compounds followed Lipinski's rule of five without any violation.