Kuzu, Burak; Hepokur, Ceylan; Algul, Oztekin

In the present study, new oxalamide-based compounds were designed from thalidomide and synthesized easily and with high yields (from 69% up to 93%) by a two-step method. The antiproliferative effects of synthesized 6a-d and 7a-d compounds on (ER+) MCF-7 and (ER-) MDA-MB-231 breast cancer cell line and human fibroblast WI-38 healthy cell line were investigated by the MTT method. The results showed that compound 7d was the most potent candidate against both MCF-7 and MDA-MB-231 cell lines with IC50 = 4.72 μM and 6.37 μM, respectively. To investigate whether antiproliferative effect of the compounds on breast cancer cell lines is dependent on COXs, expressions of COX-1/2 on the MCF-7 cell line were investigated by the Western-Blot technique. Among synthesized compounds, compound 7d increased the expression of both COX-1 and COX-2. The inhibition potential of compounds on COX-1/2 enzymes was investigated by molecular docking compared to inhibitor co-ligand celecoxib in crystal structures of COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1). Docking results indeed showed that compound 7d had a higher binding affinity for both COX-1 and COX-2 active sites. Consequently, the novel oxalamide-based compounds presented here may be important candidate molecules for the development of new COX-dependent antiproliferative agents.

Polat, M. Fatih; Anıl, Derya Aktaş

In this study, a new series consisting of 12 heteroaryl chalcone derivatives of 1,3,5-trimethoxybenzene were synthesised. Chalcones were synthesised in high purity and efficiency, via condensation of mono, bis and tris 2,4,6-trimethoxy acetophenones with hetero-2-carbaldehyde derivatives based on Claisen Schdmit condensation. The reactions feature a good scope for the all products, mild reaction conditions and good yields. The synthesized compounds were characterized by using FT-IR, NMR and elemental analysis spectroscopic techniques.

Anil, Derya Aktaş; Polat, M. Fatih

In this study, 2′,4′,6′-Trimethoxyacetophenone was reacted with various fluorine-substituted benzaldehydes in the presence of an aqueous solution of 50%-potassium hydroxide, and new chalcone derivatives in the structure of 1,3-diaryl-2-propenone comprising both fluorine and methoxy groups in the aromatic B ring were obtained in high yields under mild conditions. In base-catalyzed Claisen-Schmidt condensations, MeOH is usually used as solvent. In the condensation reactions performed with mono-fluorine-substituted benzaldehydes in MeOH, the corresponding fluorine-substituted chalcone derivatives in the B ring were synthesized in high yield. On the other hand, when di-and tri-fluorine-substituted benzaldehydes were used, it was determined that a nucleophilic aromatic substitution (SNAr) occurred in the reaction condition and the condensation yield decreased. Consequently, fluorine-methoxy substituted chalcone derivatives were isolated by substitution of fluorine and methoxy group in para position in the aromatic B ring. On the other hand, it was found that when THF was used as the reaction solvent, chalcone derivatives carrying only fluorine atoms could be obtained with excellent chemical selectivity without any competitive aromatic nucleophilic substitution (SNAr) in the condition. Particularly in the synthesis studies of such fluorine-substituted chalcones, it was determined that the Claisen-Schmidt condensation ratio is dependent on the effect of the solvent in addition to steric and electronic factors.