title: Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin.
abstract: 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 alpha,beta-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 alpha,beta-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 microM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 microM.
authors.affiliation: Chemistry Department, Faculty of Science, Taif University, Taif, Alhawyia, Kingdom of Saudi Arabia. mrea34@hotmail.com
authors.forename: Mohamed R E
authors.initials: MR
authors.lastname: Aly
authors.forename: El-Sayed I
authors.initials: el-SI
authors.lastname: Ibrahim
authors.forename: Fakher A
authors.initials: FA
authors.lastname: El Shahed
authors.forename: Hamdy A
authors.initials: HA
authors.lastname: Soliman
authors.forename: Zein S
authors.initials: ZS
authors.lastname: Ibrahim
authors.forename: Samir A M
authors.initials: SA
authors.lastname: El-Shazly
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects*; D002599:Chalcone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D011804:Quinolines; D002599:Chalcone; D004317:Doxorubicin; C037219:quinoline