SYNTHESIS, SPECTRAL AND MOLECULAR CHARACTERIZATION OF SOME NOVEL 2, 5-DISUBSTITUTED-1, 3, 4–OXADIAZOLE DERIVATIVES AND EVALUATION OF IN VIVO ANTITUMOUR ACTIVITY AGAINST HT 29 CELL LINE

Abstract

Neoplasia is a type of abnormal and excessive growth of tissue. The growth of a neoplasia is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass. The main objective of the present research work was the synthesis, characterization and evaluation of in vivo antitumour activity of some novel 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The in vivo antitumour activity of synthesized compounds was evaluated by HT 29 cell line induced malignant ascites on mouse model. The apoptosis of HT 29 cells was evaluated by using Gimsa and H33342 stain and the apoptosis ratios were analysed by FCM using AnnexinV-FITC/PI staining. The present experimental data displayed that the mortality was less in all groups except in tumour control group and all the synthesized compounds AB1-AB8 (100 mg/kg) significantly increased the PILS. While 5-FU increased the life span of 97.72%, and the PILS of synthesized compounds were found to be 45.45%, 59.09%, 68.18%, 56.81%, 38.63%, 84.09%, 77.27% and 90.90%. So the Synthesized compounds AB1-AB8 at the dose of 100 mg/kg significantly improved the overall survival of all treated animals and 5-FU was not significantly differed from each other in improving the overall survival of HT-29 cells. The apoptosis ratios of synthesized compounds were found as followed: AB1=26%; AB2=37.6%; AB3=43%; AB4=29%; AB5=24.1%; AB6=59.2%; AB7=48.2%; and AB8=63% respectively, while that of the Group-II (T. control) was 6.1%. When compared with standard drug 5-FU: 66.2%, it was indicated that compound AB8>AB6>AB7>AB3 were able to significantly induce HT-29 cells apoptosis.