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

Author:

Hricovíniová Jana,Hricovíniová Zuzana,Kozics Katarína

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.

Funder

Vedecká Grantová Agentúra MŠVVaŠ SR a SAV

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference60 articles.

1. Biological Applications of Quinazolinone Analogues: A Review

2. Quinazoline Marketed drugs—A Review;Selvam;Res. Pharm.,2011

3. Synthesis, antibacterial and antifungal activity of some novel 3-[5-(4-substituted phenyl) 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones

4. Quinazolinone and quinazoline derivatives: Recent structures with potent antimicrobial and cytotoxic activities;Jafari;Res. Pharm. Sci.,2016

5. Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline

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