Background: Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer
Objective: The anticancer activity of the target compounds was studied, via inhibition of COX-2 enzyme.
Method: A series of novel thioureas 5a-n, 8, quinazoline 6, benzo[g]quinazoline 7 and benzo[1,3] dioxole 10,
bearing a sulfonamide moiety was synthesized from the starting compound N-(2,6-dimethoxypyrimidin-4-yl)-4-
isothiocyanatobenzenesulfonamide 2. The target compounds were screened against HepG2, MCF-7, Caco-2,
HCT-116, PC-3 cancer cell lines and VERO-B normal cell line.
Results: Out of all the tested compounds, compound 5c showed a broad selective cytotoxicity against HepG2,
MCF-7, Caco-2 and PC-3 cancer cells. Moreover, a sensitization assay was performed on Caco-2 cells, and
compound 5c proved to act as a chemosensitizer for cisplatin on colon cancer (Caco-2) cells. The target compounds
were further screened in vitro for their anti COX1/COX2 activity and investigated in vivo as antiinflammatory
agents against carrageenan-induced rat paw oedema model.
Conclusion: Compound 5g showed the most selective inhibitory activity against COX-2. While, compounds 5a,
6, 5m, 5n, 5g and 5i revealed significant anti-inflammatory effect as presented in carrageenan-induced oedema
assay. Molecular docking of the tested compounds disclosed important binding modes which may be responsible
for their anticancer activity via inhibition of the COX-2 enzyme.