Discovery of natural alkaloids as potent and selective inhibitors against human carboxylesterase 2.

Human Carboxylesterase 2A (hCES2A), one of the most important serine hydrolases, plays crucial roles in the hydrolysis and the metabolic activation of a wide range of esters and amides. Increasing evidence has indicated that potent inhibition on intestinal hCES2A may reduce the excessive accumulation of SN-38 (the hydrolytic metabolite of irinotecan with potent cytotoxicity) in the intestinal tract and thereby alleviate the intestinal toxicity triggered by irinotecan. In this study, more than sixty natural alkaloids have been collected and their inhibitory effects against hCES2A are assayed using a fluorescence-based biochemical assay.

Catalyst-free visible-light-induced condensation to synthesize bis(indolyl)methanes and biological activity evaluation of them as potent human carboxylesterase 2 inhibitors.

A mild strategy for visible-light-induced synthesis of bis(indolyl)methanes was developed using aromatic aldehydes and indole as substrates. This reaction could be performed at room temperature under catalyst- and additive-free conditions to synthesize a series of bis(indolyl)methanes in good to excellent yields. In addition, all synthesized bis(indolyl)methanes together with β-substituted indole derivatives synthesized according to our previous work, were evaluated for their inhibitory effect against human carboxylesterase (CES1 and CES2).