1-Phenyl-β-carboline-3-carboxamide-1,2,3-triazole-N-phenylacetamide hybrids as new α-glucosidase inhibitors

In this work, 1-phenyl-β-carboline-3-carboxamide-1,2,3-triazole-N-phenylacetamide skeleton as a novel scaffold was designed based on hybridization of moieties that were found in the potent α-glucosidase inhibitors. Fourteen derivatives 14a-n of this scaffold were synthesized by the efficient chemical reactions. In vitro anti-α-glucosidase assay demonstrated that all the new fourteen derivatives with IC₅₀ values ranging from 64.0 to 661.4 µM were more potent than positive control acarbose with IC₅₀ value of 750.0 and in vitro kinetic study revealed that the most potent compound among them, compound 14b, was an uncompetitive α-glucosidase inhibitor. Moreover, determination of the circular dichroism (CD) spectra demonstrated that compound 14b altered the secondary structure of α-glucosidase. Prediction of the pharmacokinetics and toxicity of the most potent compound 14b showed that our new compound had good toxicity profile as an oral drug candidate. Based on these findings, compound 14b can be considered as a promising candidate for the development of a new α-glucosidase inhibitor.