Synthesis, Characterization, Computational Studies, and In vitro Evaluation of Chalcone-Quinazolinone Hybrids as Antimicrobial Agents
Amit Kumar, Sushil KumarIntroduction:
Quinazolinones are nitrogenous heterocyclic compounds discovered for their potential as antimicrobial agents. Quinazolinone ring systems are relevant to microbial applications and have been reported to show various biological activities, including antibacterial, antifungal, and anticancer properties. In this work, new chalcone-quinazolinone hybrids were synthesized, characterized, expected to exhibit antimicrobial activity, and assessed computationally.
Materials and Methods:
The chalcone-quinazolinone hybrids (A9a-g) were obtained by a series of reactions from anthranilic acid as starting material, by treating with para-aminoacetophenone, parahydroxybenzaldehyde, and benzylic/acyl chlorides. The target compounds (A9a-g) were confirmed and characterized using various techniques, including TLC, M.P., FT-IR, NMR, and mass spectrometry. Moreover, the physicochemical properties of chalcone-quinazolinone hybrids were calculated using a software program, and the similarity of the target molecules was assessed relative to ciprofloxacin and fluconazole. The in vitro biological evaluation of the compounds was performed against Gram-positive, Gram-negative, and fungal strains.
results:
The compounds A9b and A9g have shown good binding affinity against DNA gyrase and lanosterol 14α-demethylase and similarity with respect to standard drugs. Antimicrobial in vitro testing revealed that these chalcone-quinazolinone hybrids have remarkable efficacy against B. subtillis, E. coli, and C. Albicans.
Results:
The compounds A9b and A9g have shown good binding affinity for DNA gyrase and lanosterol 14α-demethylase and are similar to standard drugs. In the docking, the binding free energies are -9.4, -9.5, -8.6, -10.4, and the percentages of similarity are 61, 96, 58, 88, respectively. In vitro antimicrobial testing revealed that these chalcone-quinazolinone hybrids have remarkable efficacy against B. subtilis, E. coli, and C. albicans.
Discussion:
Computational characterization studies were conducted for the designed molecules. The compounds A9b and A9g demonstrated favourable in silico evaluations against B. subtilis, E. coli, and C. albicans, and were further synthesized, targeted, and characterized using spectral and analytical methods.
Conclusion:
Findings from molecular docking, similarity analysis, and in vitro biological evaluation indicated favourable results for chalcone-quinazolinone hybrids as antimicrobials. The synthesized target scaffolds are suitable for the development of new antimicrobial agents, particularly A9b and A9g.