Synthesis and biological evaluation of novel chalcones bearing morpholine moiety as antiproliferative agents

Authors: BEDRİYE SEDA KURŞUN AKTAR, EMİNE ELÇİN ORUÇ-EMRE, İBRAHİM DEMİRTAŞ, AYŞE ŞAHİN YAĞLIOĞLU, AYŞEGÜL KARAKÜÇÜK İYİDOĞAN, ÇAĞLAR GÜLER, ŞEVKİ ADEM

Abstract: In this research, a new series of ($E)$-3-(4-substitutedphenyl)-1-(4'-morpholinophenyl)prop-2-en-1-one derivatives 1-7 was synthesized, aiming to develop effective antiproliferative agents. The antiproliferative activities of compounds 1-7 were examined against HeLa and C6 cell lines at eight different concentrations using the BrdU ELISA assay. The activity results were compared with reference anticancer drug 5-fluorouracil (5-FU). Compound 1 had almost the same antiproliferative activity as 5-FU. Compounds 1-7 were found to have greater effects against the C6 cell line than the HeLa cell line. These compounds were also tested in order to determine their effects on enzyme activities. Compounds 2 and 3 exhibited strong activator characteristics against pyruvate kinase isoenzyme M2 (PKM2) with AC$_{50}$ values of 2.2 and 14.28 $\mu $M\textbf. Compounds 2, 3, and 7acted as inhibitors with IC$_{50}$ values in the range of 84.08-165.38 $\mu $M for carbonic anhydrase isoenzyme I (hCA I), and compounds 3 and 4 demonstrated inhibitory effects against carbonic anhydrase isoenzyme II (hCA II) with IC$_{50}$ values of 108.11 and 112.52 $\mu $M, respectively. hCA II was activated by derivatives 1, 2, 6, and 7} with AC$_{50}$ values in the range of 85.53-146.59 $\mu $M.

Keywords: Chalcone, antiproliferative activity, hCA I and II, PKM2, morpholine

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