Novel 1,2,3-triazole epicinchonas: Transitioning from organocatalysis to biological activities

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 mu M; and cholinesterase inhibition, showing activity against eqBuChE, but their main potential is for tumor anti-proliferation (showing a lowest GI(50) of 8.1 mu M). Gratifyingly, all our compounds were non-cytotoxic against the non-tumor healthy cell line, BJ-hTERT and they presented excellent simulated pharmacological properties.