Screening the protective and antioxidant potential of C-2, N-3 ring-substituted quinazolinones

Authors: Jana Hricovíniová 1    Katarína Kozics 1   
1 Ústav experimentálnej onkológie, Biomedicínske centrum, SAV, Bratislava, Slovensko   
Year: 2020
Section: Organic, bioorganic and pharmaceutical chemistry, pharmacology
Abstract No.: 1898
ISBN: 978-80-972360-6-9

Heterocyclic compounds, especially those bearing nitrogen atoms in their structures, are known for their pharmacological effects. A number of compounds have been clinically used as antibacterial, antiviral, antimalarial, anti-HIV, anti-inflammatory, anticonvulsant or anticancer drugs. Among them, quinazolinones consisting of two fused aromatic rings (benzene and pyrimidine), have been extensively studied [1]. The biological activity of quinazolinone pharmacophore could be modified by introducing appropriate substituents to this nucleus. It was shown that biological effect of individual derivatives is related to both the nature and the position of substituents [2-3].

Oxidative stress is associated with the development and progression of many diseases by damaging of cells components, including proteins, lipids, and nucleic acids. Although cells can tolerate a mild degree of oxidative stress, high levels of reactive oxygen species (ROS) can induce cell death. In such case, antioxidant agents are necessary to remove excess of ROS produced by free radical reactions. Several quinazolinone derivatives have gained a strong attention due to their activity as perspective antioxidant, anti-inflammatory and anticancer agents [4-6]. The aim of this study was to evaluate the potential antioxidant, DNA-protective and cytotoxic effects of novel differently 2,3-substituted quinazolinone derivatives in the context of their structural differences.

The experimental results have shown that studied 2,3-substituted quinazolinones QD1-QD4 are very good redox-active and DNA-protective agents. Derivatives exhibit strong antioxidant activity and reducing power. No genotoxic effects were observed in the DNA topology assay on pBR322 plasmid. Furthermore, the strong DNA-protective potential of these derivatives was detected as they were able to protect pDNA against the Fe2+-induced DNA strand breaks. Studied derivatives QD1-QD4 exhibit dose-dependent cytotoxic activity on non-malignant HaCaT cell line.

The financial support by Slovak grant agency VEGA 2/0022/18 is gratefully acknowledged.
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