Cyrhetrenyl chalcones: Synthesis, characterization and antimalarial evaluation

A new series of hybrid organometallic-organic and dinuclear organometallic chalcones containing the cyrhetrenyl fragment were synthesised and characterised. 1H and 13C NMR spectra indicate that these compounds adopt in solution an E-stereochemistry at the CC bond, as well as the s-cis conformation of the enone moiety. A similar structure was also found for 1-ferrocenyl-3-cyrhetrenyl-2-propen-1-one (2i) by X-ray crystallography in the solid state. The electron-withdrawing capability of the cyrhetrenyl group on the ketonic carbonyl and olefinic (Cβ) carbons correlate properly with the 13C shift of the carbon nuclei of the enone moiety. Evaluation of in vitro antimalarial activity of the compounds against the chloroquine-susceptible strain 3D7 and the chloroquine-resistant strain W2 of Plasmodium falciparum, indicates that these cyrhetrene conjugates are more active compared to their ferrocenic analogues.

Graphical abstractA new series of hybrid organometallic-organic and dinuclear organometallic chalcones containing the cyrhetrenyl fragment at two ends of the enone skeleton, have been synthesized and characterized. Evaluation of in vitro antimalarial activity indicates that the cyrhetrene conjugates are more active than their ferrocenic analogues.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Cyrhetrenyl-organic and Cyrhetrenyl-ferrocenyl chalcones have been designed and prepared. ► The compounds adopt an E-stereochemistry at the CC bond and s-cis conformation of the enone moiety. ► Cyrhetrenyl chalcones possess a more potent antiplasmodial activity than their ferrocenyl analogues.