Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with
inflammation, the additional involvement of COX-2
enzyme with
cancer activity was recently discovered. In some
cancer types the level of COX-2
enzyme is increased indicating that this
enzyme could be a suitable target for
cancer therapy. Based on these findings, we have synthesized some new
diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against
androgen-independent prostate
adenocarcinoma (PC-3), colon
carcinoma (HCT-116), human
breast cancer (T47D),
breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the
diflunisal and
thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the
breast cancer cell line T47D, whereas compounds 6 and 10 which are
thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116
cancer cell line with the tested
thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the
diflunisal and
thiosemicarbazide functionalities potentiate anticancer activity on
prostate cancer and the
thiosemicarbazide functionality decreases the anticancer activity of
diflunisal on
colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2
enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2
isozyme over COX-1, which is in agreement with the experimental results.