Synthesis, characterization, antitubercular and antibacterial activity, and molecular docking of 2,3-disubstituted quinazolinone derivatives

Abstract:

Quinazolinone derivatives, which are known for their versatile biological activities, have been reported to show significant antibacterial and antitubercular activities. Fourteen compounds that belong to either 2-methyl substituted quinazolinone or 2-phenyl substituted quinazolinones were synthesized. Compounds 5a–e and 8a–c showed a minimum inhibitory concentration value between 6.25 and 100 μg/mL against Mycobacterium tuberculosis. Compounds 5g and 8d, on the other hand, showed significant antibacterial activity against Staphylococcus albus and Streptococcus pyogenes. The use of amido, thioamido, imidamido, N,N-dimethyl guanidinyl, or N-pyridoyl substituents at 3-position of quinazolinone was found to increase antitubercular activity. A binding affinity prediction by autodock vina was higher for the 2-phenyl series, which may be due to increased hydrophobic interactions within the binding site of enoyl-acyl carrier protein reductase.

Keywords::

• quinazolinones
• antitubercular activity
• antibacterial activity
• autodock vina

Acknowledgments

The authors are grateful for the material support received from Sri Padmavathi School of Pharmacy and University of Gondar. The authors are also grateful for the authorities of UCSF chimera, PyRx, and PyMOL for providing free software.

Disclosure

The authors report no conflicts of interest in this work.