Search for Non-Protein Protease Inhibitors Constituted with an Indole and Acetylene Core

寻找以吲哚和乙炔为核心的非蛋白蛋白酶抑制剂

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作者:Marco A Almaraz-Girón, Ernesto Calderón-Jaimes, Adrián Sánchez Carrillo, Erik Díaz-Cervantes, Edith Castañón Alonso, Alejandro Islas-Jácome, Armando Domínguez-Ortiz, Sandra L Castañón-Alonso

Abstract

A possible inhibitor of proteases, which contains an indole core and an aromatic polar acetylene, was designed and synthesized. This indole derivative has a molecular architecture kindred to biologically relevant species and was obtained through five synthetic steps with an overall yield of 37% from the 2,2'-(phenylazanediyl)di(ethan-1-ol). The indole derivative was evaluated through docking assays using the main protease (SARS-CoV-2-Mpro) as a molecular target, which plays a key role in the replication process of this virus. Additionally, the indole derivative was evaluated as an inhibitor of the enzyme kallikrein 5 (KLK5), which is a serine protease that can be considered as an anticancer drug target.

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