Abstract
A small family of novel modular monofunctional epicinchonidine-1,2,3-triazole compounds was prepared in very good overall yield (3 steps from cinchonidine, 49–87% yield) using simple Cu(I) catalyzed click-chemistry. The objective of this study was to access their hitherto unknown catalytic role in some key organic reactions like: ketimine hydrosilylation, Michael-addition and the Biginelli reaction. This is the first report on the application of cinchonidine derived 1,2,3-triazoles in organocatalysis, and includes catalytic screening and preliminary Density Functional Theory (DFT) mechanistic studies. The new compounds were screened for antimalarial activity against Plasmodium falciparum (W2 strain), exhibiting IC50 values in the range 2.0–6.8 µM; and cholinesterase inhibition, showing activity against eqBuChE, but their main potential is for tumor anti-proliferation (showing a lowest GI50 of 8.1 µM). Gratifyingly, all our compounds were non-cytotoxic against the non-tumor healthy cell line, BJ-hTERT and they presented excellent simulated pharmacological properties.
Graphical Abstract
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Supporting information
Full experimental details that include 1H and 13C NMR spectra, computational studies and bioassays can be found via the “Supplementary Content” section of this article’s webpage.
Acknowledgments
Dr. Olivia Furtado of the Laboratorio Nacional de Energia e Geologia (LNEG), is acknowledged for the optical rotation measurements. Chiratecnics thanks the University of Evora for laboratory space and other supports. Prof. Maurizio Benaglia (Dept of Chemistry, University of Milan) is acknowledged for very helpful discussions on part of this work.