Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies.

Abstract

Two novel series of quinazolinone based isoxazole and isoxazoline hybrid compounds were synthesized from 6-aminoquinazolinone as a key precursor. The title compounds were achieved in synthetic routes via propargylation and allylation reactions of the precursor followed by cyclization with various chloroximes. The new compounds 4a-g and 6a-g were screened for their antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria and two fungi by employing Ampicillin and Itraconazole as standard reference. Among all, the 4-bromosubstituted analogues in isoxazole series 4d and in isoxazoline series 6d demonstrated potent activity against all bacterial and fungal strains compared to Ampicillin as well as Itraconazole. The MIC of these compounds were determined as 0.012 μM. The antioxidant investigation revealed that compounds 4f and 6f with dimethyl substitution, exhibited significant activity. Their respective IC₅₀ values were 1.28 ± 0.33, 1.39 ± 0.38 µM and 1.07 ± 0.24, 1.10 ± 0.26 µM, when compared to Ascorbic acid. The compounds 4 g and 6 g with dichloro substitution, exhibited promising results with IC₅₀ values were 2.72 ± 0.34 µM and 2.78 ± 0.41 µM for 4 g, and 2.24 ± 0.93 µM and 2.45 ± 0.53 µM for 6 g, respectively. Their antimicrobial and antioxidant activities were authenticated by the molecular docking study against crystal structure of DNA gyrase and NADPH oxidase. The predicted ADME properties of these molecules progressed favourable drug-likeness properties.