SYNTHESIS OF SOME QUINOLINYL CHALCONE ANALOGUES AND INVESTIGATION OF THEIR ANTICANCER AND SYNERGISTIC ANTICANCER EFFECT WITH DOXORUBICIN
©2012 Mohamed R. E. Aly1,#, El-Sayed I. Ibrahim2, Fakher A. El Shahed2, Hamdy A. Soliman2, Zein S. Ibrahim3, Samir A. M. El-Shazly4
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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