Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study

Abstract

The evaluation of antioxidant compounds that counteract the mutagenic effects caused by the direct action of reactive oxygen species on DNA molecule is of considerable interest. Therefore, a series of 2,3-substituted quinazolinone derivatives (Q1–Q8) were investigated by different assays, and the relationship between their biological properties and chemical structure was examined. Genotoxicity and the potential DNA-protective effects of Q1–Q8 were evaluated by comet assay and DNA topology assay. Antioxidant activity was examined by DPPH-radical-scavenging, reducing-power, and total antioxidant status (TAS) assays. The cytotoxic effect of compounds was assessed in human renal epithelial cells (TH-1) and renal carcinoma cells (Caki-1) by MTT assay. Analysis of the structure–activity relationship disclosed significant differences in the activity depending on the substitution pattern. Derivatives Q5–Q8, bearing electron-donating moieties, were the most potent members of this series. Compounds were not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants (H2O2, Fe2+ ions). Furthermore, compounds exhibited higher cytotoxicity in Caki-1 compared to that in TH-1 cells. Substantial antioxidant effect and DNA-protectivity along with the absence of genotoxicity suggested that the studied quinazolinones might represent potential model structures for the development of pharmacologically active agents.

A comprehensive review of recent advances in the biological activities of quinazolines

“…A new set of 2,3-disubstituted quinazolinone analogues 32 was developed and examined for biological activity (Hricoviniova et al, 2021). Antioxidant activity GOMAA was tested using the total antioxidant status (TAS), DPPHradical-scavenging, and reducing power assays.…”

KOtBu Mediated Alcohol Dehydrogenation Strategy: Synthesis of 2‐Aryl Quinazolinones

“…Quinazolinones are nitrogen‐containing fused heterocycles that show a close resemblance to natural alkaloids, owning to these quinazolinone scaffolds have been employed extensively in synthetic drugs . Functionalized quinazolinone derivatives are largely used in pharmaceutical industries (see Figure 1), [1] particularly as anti‐HIV, [2] antifungal, [3] anti‐inflammatory, [4] anti‐cancer, [5] antimutagenic agents, [6] etc. Several substituted quinazolinone also serve as ligands, as well as DNA binders [7] .…”

synthesis and characterization of Pyrimidine from chalcone as a polymeric prodrug with fusidic acid and ZnO and study bioactivity

“…Despite the abundance of pyrimidine-based antioxidants, only a small number of them are therapeutically employed because of their side effects. (13,14). Fusidic acid (FA) in Figure 5, with a pyrimidine ring as a polymer, plays an important role as an antioxidant, Fusidic acid is an antibiotic that belongs to a group of its own-the fusidate It was obtained from cultures of a fungus, Fusidium coccineum, which was originally isolated from monkey feces.…”