Chapter 6 - Natural Products as Cathepsin Inhibitors

https://doi.org/10.1016/B978-0-444-63749-9.00006-2Get rights and content

Abstract

Cathepsins are proteases found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, their catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Cathepsins have been identified as therapeutic targets in the search for new drugs against a number of human pathologies, including cancer, Alzheimer's, and osteoporosis.

A number of natural products have been reported as selective inhibitors of some cathepsins. Chemical structure of natural products as inhibitors of cathepsins can be very diverse. Some peptidic natural products are inhibitors of the cysteine protease cathepsins such as E-64 isolated from Aspergillus, which is a cathepsin B inhibitor, or more recently the marine cyanobacterial metabolite gallinamide A which is a selective inhibitor of human cathepsin L. Also amino acid derivatives have been reported as inhibitors of cathepsin A.

Other natural products include chalcone natural products possessing cytotoxic activities against prostate cancer cells and inhibiting cysteine cathepsins in vitro, antipain and its analogues isolated from Streptomyces as inhibitors of cathepsin K, and natural biflavones as novel inhibitors of cathepsins B and K.

In this review we will report the most representative examples of natural products as inhibitors of cathepsins, especially the ones reported during the last decade.

Keywords

Cathepsins
Depsipeptides
Flavonols
Inhibitors
Terpenes

Cited by (0)

View Abstract