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Novel Thiourea Derivatives Bearing Sulfonamide Moiety as Anticancer Agents Through COX-2 Inhibition

[ Vol. 17 , Issue. 10 ]


Mostafa M. Ghorab*, Mohamed S.A. El-Gaby, Mansour S. Alsaid, Yaseen A.M.M. Elshaier, Aiten M. Soliman , Fardous F. El-Senduny , Farid A. Badria and Abdelrahman Y.A. Sherif   Pages 1411 - 1425 ( 15 )


Background: Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer activity.

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.


Thiourea, pyrimidine, sulfonamide, cytotoxicity, COX-2, docking.


Department of Pharmacognosy, College of Pharmacy, King-Saud University, P.O. Box 2457, Department of Organic Chemistry, Faculty of Science, Al-Azhar University, Assuit, Department of Pharmacognosy, College of Pharmacy, King-Saud University, P.O. Box 2457, Riyadh 11451, Department Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assuit, Department of Drug Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Department of Chemistry, Faculty of Science, Mansura University, Mansura, Department of Pharmacognosy, Faculty of Pharmacy, Mansura University, Mansura, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh

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