Inhibition of human cathepsins B and L by caffeic acid and its derivatives

Ulčakar, Liza (author), Novinec, Marko (author)

Caffeic acid (CA) and its derivatives caffeic acid phenethyl ester (CAPE) and chlorogenic acid (CGA) are phenolic compounds of plant origin with a wide range of biological activities. Here, we identify and characterize their inhibitory properties against human cathepsins B and L, potent, ubiquitously expressed cysteine peptidases involved in protein turnover and homeostasis, as well as pathological conditions, such as cancer. We show that CAPE and CGA inhibit both peptidases, while CA shows a preference for cathepsin B, resulting in the strongest inhibition among these combinations. All compounds are linear (complete) inhibitors acting via mixed or catalytic mechanisms. Cathepsin B is more strongly inhibited at pH 7.4 than at 5.5, and CA inhibits its endopeptidase activity preferentially over its peptidyl-dipeptidase activity. Altogether, the results identify the CA scaffold as a promising candidate for the development of cathepsin B inhibitors, specifically targeting its endopeptidase activity associated with pathological proteolysis of extracellular substrates.

• Language: English
• Keywords: enzyme inhibition, proteolysis, peptidase, catalytic inhibition, mixed inhibition, chlorogenic acid, caffeic acid phenethyl ester
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 9 str.
• Numbering: Vol. 11, iss. 1, art. 31
• PID: 20.500.12556/RUL-134780
• UDC: 577.15
• ISSN on article: 2218-273X
• DOI: 10.3390/biom11010031
• COBISS.SI-ID: 45685763
• Publication date in RUL: 01.02.2022

Record is a part of a journal

• Title: Biomolecules
• Shortened title: Biomolecules
• Publisher: MDPI
• ISSN: 2218-273X
• COBISS.SI-ID: 519952921

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.01.2021

Secondary language

• Language: Slovenian
• Keywords: inhibicija encimov, proteoliza, peptidaza, katalitična inhibicija, mešana inhibicija, klorogenska kislina, fenetilni ester kavne kisline

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0140
• Name: Proteoliza in njena regulacija