Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives
| Autor: | Renato Moreira Rosa, Valéria Rodrigues Pinhatti, Selma da Silva Santos, Maria Lúcia Scroferneker, Juliana da Silva, Jenifer Saffi, Dinara Jaqueline Moura, Cheila Denise Ottonelli Stopiglia, João Antonio Pêgas Henriques, Tales Leandro Costa Martins, Izabel Vianna Villela, Carlos Renato Machado |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Antifungal Agents DNA damage Health Toxicology and Mutagenesis Trypanosoma cruzi medicine.disease_cause Cell Line Toxicology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetulus In vivo Genetics medicine Animals Humans Cytotoxicity Mutagenicity Tests Hydrazones Biological activity Trypanocidal Agents In vitro Comet assay 030104 developmental biology chemistry Biochemistry 030220 oncology & carcinogenesis Comet Assay Lipid Peroxidation DNA Genotoxicity DNA Damage Mutagens |
| Zdroj: | Mutation research. Genetic toxicology and environmental mutagenesis. 806 |
| ISSN: | 1879-3592 |
| Popis: | Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. |
| Databáze: | OpenAIRE |
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