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Comparative study of the cytotoxicity and genotoxicity of kaurenoic acid and its semi-synthetic derivatives methoxy kaurenoic acid and kaurenol in CHO-K1 cells.

Cano, Bruno Limonti; Moreira, Monique Rodrigues; Goulart, Mirian Oliveira; Dos Santos Gonçalves, Natália; Veneziani, Rodrigo Cassio Sola; Bastos, Jairo Kenupp; Ambrósio, Sérgio Ricardo; Dos Santos, Raquel Alves.
Food Chem Toxicol; 102: 102-108, 2017 Apr.
Inglês | MEDLINE | ID: mdl-28167160
The diterpene kaurenoic acid (KA) has vasorelaxant, antimicrobial, anti-tumoural and anti-leishmanial effects. Semi-synthetic derivatives were obtained to achieve more satisfactory responses. The assessment of genotoxicity is part of the toxicological evaluation of therapeutic compound candidates. The present study investigated the cytotoxicity and genotoxicity of KA and its semi-synthetic derivatives methoxy kaurenoic acid (MKA) and kaurenol (KRN) using the CHO-K1 cell line. The cytotoxicity evaluation demonstrated that treatments with 200 and 400 µM KA reduced cellular proliferation to 36.5 and 4.43%, respectively, and that 100 and 200 µM KA reduced the survival fraction (SF) to 48.1 and 5.5%, respectively. MKA and KRN at concentrations of 400 µM reduced proliferation to 81 and 86.8%, respectively, while 100 and 200 µM KRN reduced the SF to 50%, and 200 µM MKA reduced the SF to 74%. No genotoxicity was observed for KA or MKA. However, 100 µM KRN increased the DNA damage index, as detected by comet assay, although a micronucleus assay did not confirm these data. The results demonstrated that KA and its semi-synthetic derivative MKA were not genotoxic when tested at noncytotoxic concentrations, but KRN was genotoxic at the highest concentration that was tested, as demonstrated by the comet assay.