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

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 com- pounds were screened for antimalarial activity against Plasmodium fal- ciparum (W2 strain), exhibiting IC50 values in the range 2.0–6.8mM; and cholinesterase inhibition, showing activity against eqBuChE, but their main potential is for tumor anti-proliferation (showing a lowest GI50 of 8.1 mM). Gratifyingly, all our compounds were non-cytotoxic against the non-tumor healthy cell line, BJ-hTERT and they presented excellent simulated pharmacological properties.