BIOLOGICAL STUDIES OF THE EFFECT OF SOME NEW SYNTHETIC TRIAZOLE DERIVATIVES ON EHRLICH ASCITES CARCINOMA CELLS
The importance of triazole derivatives lies in the field of organic or pharmaceutical chemistry that they have occupied a unique position in heterocyclic chemistry, due to its various biological activities. The aim of our study is to determine the bioactivity (evaluation of the anti-tumor and anti-oxidant activity ) of the following trizole derivatives: (S19) 7-(benzylamino)- 2-(ethylthio)-6-formyl-5-oxo-1-phenyl-1,5-dihydro-]1,2,4[triazolo]1,5-a[pyridine-8-carbonitrile and (S18) 2-(ethylthio)-6- formyl-7-(isobutylamino)-5-oxo-1-phenyl-1,5-dihydro-1,2,4[triazolo]1,5-a[pyridine-8-carbonitrile. The new synthesized compounds will be investigated for their toxicity and applied on an experimental carcinogenesis model in order to evaluate its antitumor potential and anti-oxidant effect; against animal carcinogenesis "Ehrlich carcinoma)" (EAC). It was found that S91 & S18 were safe compounds; also these compounds increase life span of treated animals. Administration of S91 (5mg/kg I.P.) and S18 (5 mg/kg, I.P) results in a significant reduction in the volume of EAC by 59% and 64% and in the count of EAC cells by 34% and 47% in S91 and S18 treated groups; respectively. An anti-oxidant effect of S91 and S18 in vivo was observed; the results investigate a significant decrease in malodialdehyde by 66.66% & 71.6% & interlukin-6 levels by 6.8% & 23% in S91 and S18 treated groups; respectively compared to positive control group. While, results showed a significant increase in superoxide dismutase activity, catalase activity, and glutathione reduced levels. While these compounds showed hepatotoxicity which indicated that by an increases in ALT and AST activities, and slight changes in kidney functions. Triazole is a unique template that is associated with several biological activities. The anti-tumor mechanisms may be mediated by preventing oxidative damage and improved animal chances of survival. The results of clinical trials will be needed to spur the development of triazole derivatives as cancer therapeutic agents.