Synthesis and anticancer activity of long chain substituted 1,3,4-oxadiazol-2-thione, 1,2,4-triazol-3-thione and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives

Abstract

In this paper, three novel series of 5-long chain alkenyl/hydorxyalkenyl-1,3,4-oxadiazol-2-thiones 2(a–d), 4-amino-5-long chain alkenyl/hydroxyalkenyl-1,2,4-triazol-3-thiones 3(a–d) and 3-long chain alkenyl/hydroxyalkenyl-6-phenyl-(7H)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines 4(a–d) were synthesized with an aim to produce promising anticancer agents. We describe here the synthesis of compounds 2(a–d), 3(a–d) and 4(a–d) using long chain alkenyl/hydroxyalkenyl hydrazides 1(a–d) as starting material. Our investigation shows that the thione tautomer of 2(a–d) and 3(a–d) dominates. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. After characterization, all compounds were tested for in vitro anticancer activity against PBMCs and three different human cancer cell lines. On the basis of SAR, it may be concluded that the potency of drugs depends on the nature of FA chain and the heterocyclic ring system. Among all the tested compounds, compounds having fused ring system (triazolothiadiazine nucleus) and the hydroxyl group attached to the FA chain (4c and 4d) were found to be the most promising anticancer agents.