Molecules, Vol. 24, Pages 4077: Synthesis, Structure and In Vitro Cytotoxic Activity of Novel Cinchona —Chalcone Hybrids with 1,4-Disubstituted- and 1,5-Disubstituted 1,2,3-Triazole Linkers
Molecules, Vol. 24, Pages 4077: Synthesis, Structure and In Vitro Cytotoxic Activity of Novel Cinchona—Chalcone Hybrids with 1,4-Disubstituted- and 1,5-Disubstituted 1,2,3-Triazole Linkers
Molecules doi: 10.3390/molecules24224077
Authors:
Jernei
Duró
Dembo
Lajkó
Takács
Kőhidai
Schlosser
Csámpai
By means of copper(I)-and ruthenium(II)-catalyzed click reactions of quinine- and quinidine-derived alkynes with azide-substituted chalcones a systematic series of novel cinchona-chalcone hybrid compounds, containing 1,4-disubstituted- and 1,5-disubstituted 1,2,3-triazole linkers, were synthesized and evaluated for their cytotoxic activity on four human malignant cell lines (PANC-1, COLO-205, A2058 and EBC-1). In most cases, the cyclization reactions were accompanied by the transition-metal-catalyzed epimerization of the C9-stereogenic centre in the cinchona fragment. The results of the in vitro assays disclosed that all the prepared hybrids exhibit marked cytotoxicity in concentrations of low micromolar range, while the C9-epimerized model comprising quinidine- and (E)-1-(4-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)phenyl) fragments, connected by 1,5-disubstituted 1,2,3-triazole linker, and can be regarded as the most potent lead of which activity is probably associated with a limited conformational space allowing for the adoption of a relatively rigid well-defined conformation identified by DFT modelling. The mechanism of action of this hybr...
Source: Molecules - Category: Chemistry Authors: Jernei Dur ó Dembo Lajk ó Tak ács K őhidai Schlosser Cs ámpai Tags: Article Source Type: research