SYNTHESIS OF SOME QUINOLINYL CHALCONE ANALOGUES AND INVESTIGATION OF THEIR ANTICANCER AND SYNERGISTIC ANTICANCER EFFECT WITH DOXORUBICIN

©2012 Mohamed R. E. Aly^1,#, El-Sayed I. Ibrahim², Fakher A. El Shahed², Hamdy A. Soliman², Zein S. Ibrahim³, Samir A. M. El-Shazly⁴

^#Phone: 00966562694753; e-mail: [email protected]

¹Chemistry Department, Faculty of Science, Taif University, Taif, Alhawyia, Kingdom of Saudi Arabia; Chemistry Department, Faculty of Applied Science, Port Said University, Port Said-Egypt;
²Chemistry Department, Faculty of Science, Suez Canal University, Ismailia-Egypt;
³Physiology Department, Faculty of Medicine, Taif University, Taif-KSA; Department of Physiology, Faculty of Veterinary Medicine, KaferelSheikh University, Egypt;
⁴Biotechnology Department, Faculty of Science, Taif University, Taif-KSA; Department of Biochemistry, Faculty of Veterinary Medicine, KaferelSheikh University, Egypt

Received May 18, 2011; in final form 27.07.2011

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa,b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va,b) were further manipulated into cyclic α,β-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI-VII). Deethoxycarboxylation of derivatives (VIIa,b) afforded cyclohexenons (VIIIa,b) allowing formation of a mini library of α,β-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open β-enones, (Vb) and (Ve), showed significant anticancer activity with IC₅₀ of 5.0 and 2.5 μM respectively. Only one cyclic β-enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 μM.

Keywords: quinoline, chalcones, doxorubicin, antiproliferativ effect, synergistic effect.

Биоорг.химия 2012, 38 (4): 489-495