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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

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

Author(s): 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

Volume 17, Issue 10, 2017

Page: [1411 - 1425] Pages: 15

DOI: 10.2174/1871520617666170327153735

Price: $65


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.

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

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