ABSTRACT
Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in µg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.
Subject(s)
Carbohydrates/chemistry , Cell Proliferation/drug effects , Coordination Complexes/chemistry , Gold/chemistry , Carbohydrates/administration & dosage , Carbohydrates/chemical synthesis , Cisplatin/administration & dosage , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Fibroblasts/drug effects , Fibroblasts/pathology , Gold/administration & dosage , HeLa Cells , Humans , Ligands , Lung/drug effects , Lung/pathology , MCF-7 Cells , Magnetic Resonance Spectroscopy , Rifampin/administration & dosage , Structure-Activity RelationshipABSTRACT
Bixin is a carotenoid found in the seeds of Bixa orellana L., a plant native to tropical America that is used in the food industry. The aim of this study was to investigate the effect of bixin on DNA damage and pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in the liver and colon of Wistar rats. The animals received bixin at daily doses of 0.1, 1.0 and 10mg/kg body weight (bw) by gavage. For the assessment of DNA damage in hepatocytes and colon cells with the comet assay, the administration of bixin was for 7 days. The animals received a single subcutaneous injection of 25mg/kg bw of DMH, and were euthanized 4h later. For the evaluation of the frequency of aberrant crypt foci (ACF), the animals were treated with the different doses of bixin for 4 weeks. Four doses of 40mg/kg bw DMH, two doses in the first week and two doses in the second week, were administered and euthanasia occurred at 4 weeks after the beginning of treatment. Bixin reduced the frequency of DNA damage in hepatocytes at the highest two doses tested (1.0 and 10mg/kg bw). On the other hand, no differences in the frequency of DNA damage in colon cells were observed between animals treated with bixin plus DMH and those treated with DMH alone. In addition, the frequency of ACF did not differ significantly between the group treated with bixin plus DMH and the DMH group. The results suggest that bixin does not suppress the formation of ACF, indicating the absence of a protective effect against colon carcinogenesis.
