| Autor: |
Véras JH; Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil., Do Vale CR; Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil., Luiz Cardoso Bailão EF; Laboratory of Biotechnology, Henrique Santillo Campus, State University of Goiás, Anápolis, Brazil., Dos Anjos MM; Chemistry Institute, Federal University of Goiás, Goiânia, Brazil., Cardoso CG; Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil., de Oliveira MG; School of Pharmacy, Federal University of Goiás, Goiânia, Brazil., de Paula JR; School of Pharmacy, Federal University of Goiás, Goiânia, Brazil., de Oliveira GR; Chemistry Institute, Federal University of Goiás, Goiânia, Brazil., Silva CRE; Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil., Chen-Chen L; Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil. |
| Abstrakt: |
Coumarins and chalcones are compounds widely found in plants or obtained by synthetic methods which possess several biological properties including antioxidant, anti-inflammatory, and antitumor effects. A series of coumarin-chalcone hybrids were synthesized to improve their biological actions and reduce potential adverse effects. Considering the applications of these molecules, a coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl) acryloyl-2 H-chromen-2-one] (4-MET) was synthesized and the genotoxic, cytotoxic, and protective effects assessed against damage induced by different mutagens. First, in silico tools were used to predict biological activity of 4-MET which indicated a chemopreventive potential. Subsequently, the genotoxic/antigenotoxic activities of 4-MET were determined both in vitro (Ames test) and in vivo (micronucleus (MN) test and comet assay). In addition, molecular docking simulations were performed between 4-MET and glutathione reductase, an important cellular detoxifying enzyme. Our results indicated that 4-MET was not mutagenic in the Ames test; however, when co-treated with sodium azide or 4-nitroquinoline 1-oxide (4-NQO), 4-MET significantly reduced the harmful actions of these mutagens. Except for a cytotoxic effect after 120 hr treatment, 4-MET alone did not produce cytotoxicity or genotoxicity in the MN test and comet assay. Nonetheless, all treatments of 4-MET with cyclophosphamide (CPA) showed a chemoprotective effect against DNA damage induced by CPA. Further, molecular docking analysis indicated a strong interaction between 4-MET and the catalytic site of glutathione reductase. These effects may be related to (1) damage prevention, (2) interaction with detoxifying enzymes, and (3) DNA-repair induction. Therefore, data demonstrated that 4-MET presents a favorable profile to be used in chemopreventive therapies. |
