Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study
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 re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/610 |
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| author | Jana Hricovíniová Zuzana Hricovíniová Katarína Kozics |
| author_facet | Jana Hricovíniová Zuzana Hricovíniová Katarína Kozics |
| author_sort | Jana Hricovíniová |
| collection | DOAJ |
| description | 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 (H<sub>2</sub>O<sub>2</sub>, Fe<sup>2+</sup> 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. |
| first_indexed | 2024-03-09T05:24:58Z |
| format | Article |
| id | doaj.art-15d94d55e7f448a9962cc225c6cf2177 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:24:58Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-15d94d55e7f448a9962cc225c6cf21772023-12-03T12:36:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122261010.3390/ijms22020610Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship StudyJana Hricovíniová0Zuzana Hricovíniová1Katarína Kozics2Cancer Research Institute BMC, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, SlovakiaInstitute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38 Bratislava, SlovakiaCancer Research Institute BMC, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, SlovakiaThe 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 (H<sub>2</sub>O<sub>2</sub>, Fe<sup>2+</sup> 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.https://www.mdpi.com/1422-0067/22/2/610quinazolinonesantioxidant potentialgenotoxicitycytotoxicitystructure—activity relationships |
| spellingShingle | Jana Hricovíniová Zuzana Hricovíniová Katarína Kozics Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study International Journal of Molecular Sciences quinazolinones antioxidant potential genotoxicity cytotoxicity structure—activity relationships |
| title | Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study |
| title_full | Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study |
| title_fullStr | Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study |
| title_full_unstemmed | Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study |
| title_short | Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study |
| title_sort | antioxidant cytotoxic genotoxic and dna protective potential of 2 3 substituted quinazolinones structure activity relationship study |
| topic | quinazolinones antioxidant potential genotoxicity cytotoxicity structure—activity relationships |
| url | https://www.mdpi.com/1422-0067/22/2/610 |
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