In our present study author has synthesized novel derivatives of 1, 3, 4-oxadiazoles by linear synthetic method and characterized the compounds by LCMS, 1H-NMR and 13C spectral analysis. In this research work 2-(4-t-butyl-phenyl)-5-(5-aryl substituted-[1, 3, 4] oxadiazol-2-yl)-pyridine have been synthesized by the oxidative cyclization reaction and purified by column-chromatography. The 6-(4-t-butyl-phenyl)-nicotinic acid hydrazide which upon reacted with aldehydes (a-f) and got the Schiff base derivatives. The compounds 7a-7f were screened for MTT assay against HeLa, MCF7and Caco-2 Cell lines. A graph was plotted against percentage viability and concentration of the compounds and obtained the IC50 values. Among the synthesized novel derivatives of 1, 3, 4-oxdiazoles two compounds 7b and 7d exhibited good cytotoxicity on MCF7 cell lines having an IC50 of 6.74µM and 3.69 µM respectively. On Caco-2 cell lines the compounds 7c, 7d and 7f have showed moderate cytotoxicity having IC50 of 24.6µM, 55.5µM and 24.8µM respectively.