DNA Repair Capability of MCF-7 after Exposure to Substituted Benzofuran Derivatives with Aromatase Inhibitory Effects

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Pharmacology And Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Associate Professor, Department of Medicinal Chemistry And Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Professor, Department of Pharmacology And Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

4 MSc Student, Department of Pharmacology And Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Benzofuran derivatives block the aromatase enzyme and reduce estrogen production. It was shown that although the cytotoxicity of these compounds could be in part due to the aromatase inhibition, DNA damage may also be involved. This study was designed to assess whether these derivatives can induce DNA damage, and to evaluate if such damage could be repaired.Methods: MCF-7 cells were exposed to the compounds at different concentrations to find a concentration sufficient to induce DNA damage. Cells were exposed for 2 hours to genotoxic concentration of compounds and recovered for 17 and 24 hours. The comet assay was used to examine DNA damage. Analysis of variance (ANOVA) followed by Tukey's test were used for statistical analysis at a significance level of P < 0.05.Findings: The genotoxic effects of benzofuran derivatives were observed in 70, 75, and 200 nM for the 4-fluoro, 4-chloro, and 2-methoxy derivatives of benzofuran, respectively. The genotoxic concentration of 2-methyl derivatives and the unsubstituted derivatives of benzofuran were 300 and 1000 nM, respectively. The DNA damages caused by 4-fluoro, 4-chloro and 2-methyl derivatives of benzofuran recovered after 24 hours while those caused by 2-methoxy and unsubstituted derivatives of benzofuran recovered after 17 hours. Conclusion: The benzofuran phenylmethyl imidazole and its 4-fluoro, 4-chloro, 2-methoxy, and 2-methyl derivatives are genotoxic. Moreover, our study showed that the DNA damages caused by these substances were repairable. Therefore, if these compounds are able to pass other safety and clinical tests, they could be used as new therapeutic compounds.

Keywords

References

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Journal of Isfahan Medical School
Volume 29, Issue 151 - Serial Number 151
July and August 2011
Pages 1183-1193

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History

  • Receive Date: 12 October 2011
  • Revise Date: 03 May 2024
  • Accept Date: 06 April 2022

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