Facile synthesis and cytotoxic activity of 3,6-disubstituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles

Abstract

Afacile synthesis of 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles (5a-j) has been achieved by condensing 3-aryl substituted 4-amino-5-mercapto (4H)-1,2,4-triazole (4a-b) with various aromatic acids. The structures of the synthesized compounds were supported by IR, 1H NMR, mass spectral data and elemental analysis The compounds were evaluated for in vitro cytotoxic activity against four human cancer cell lines: two ovarian (PA-1and OAW-42) and two breast (T47D and MCF-7) cell lines using the methyl thiazol tetrazolium assay method. It showed that some of the tested compounds 5a, 5b, 5g and 5f exhibited significant activity against PA-1 cell lines and the compounds 5a and 5e exhibited IC50 of 0.72 µM and 0.65 µM, respectively, against the cell lines of MCF-7, which are close to Doxorubin. After comparing the cytotoxic activity results of compounds 5a-j, it was concluded that the incorporation of triazolo-thiadiazole moiety in aryl propionic acid group gives rise to enhanced anticancer activity. Also, the substitution of chloro group in the aryl ring at the 3rd position was found to enhance their potency.