Synthesis and Evaluation of In-vitro and In-vivo Antioxidant Properties: Novel 2-phenyl-3-Sustituted Quinazoline-4-ones

Quinazolinones, a prominent scaffold in medicinal chemistry, exhibits a wide array of biological activities. This research focused on synthesizing and evaluating two series of 3-substituted quinazolin-4(3H)-ones for their antioxidant properties. The evaluation encompassed both in vitro methods, namely DPPH and reducing power method, and in vivo studies using lipid peroxidation, superoxide dismutase (SOD), catalase, glutathione reductase, and glutathione peroxidase assays on erythrocytes of carbon tetrachloride-intoxicated rats. The objective was to establish structure-antioxidant activity relationships based on diverse substituents at position 3 of the quinazolinone scaffold. The newly synthesized quinazoline derivatives, designated as 7a1-7a8 and 7b1-7b8, displayed notable antioxidant properties, potentially contributing to their observed biological activity. Among the two series, compound 7b5, bearing a methyl piperazine at the 3rd position and a chlorine atom at the 6th position on the 3-substituted quinazoline nucleus, exhibited outstanding antioxidant activity in both in vitro and in vivo methods. Furthermore, compounds 7a5 and 7a8 demonstrated significant antioxidant properties in the DPPH assay, while compounds 7a3, 7a4, 7a5, and 7a8 displayed notable activity in the reducing power method. In vivo studies revealed significant antioxidant properties in compounds 7a5, 7a8, 7b4, 7b6, and 7b8. Additionally, compounds 7a6 and 7b7 showed promising antioxidant activity in vivo. These findings underscore the potential of quinazoline-based compounds as therapeutic agents for managing oxidative stress-related disorders.