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

Molecules. 2021 Jun 23;26(13):3817. doi: 10.3390/molecules26133817.

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.

Keywords: KLK5 protease; SARS-CoV-2-Mpro; docking studies; indole derivatives; inhibitor of proteases; studies in silico; synthesis.

MeSH terms

  • Acetylene / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • COVID-19 Drug Treatment
  • Coronavirus 3C Proteases / antagonists & inhibitors
  • Drug Discovery
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Indoles / chemistry*
  • Kallikreins / antagonists & inhibitors
  • Models, Molecular
  • Molecular Docking Simulation
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / enzymology*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Indoles
  • Protease Inhibitors
  • KLK5 protein, human
  • Kallikreins
  • Coronavirus 3C Proteases
  • Acetylene