Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Mining a cathepsin inhibitor library for new antiparasitic drug leads.

  • Author(s): Ang, Kenny KH
  • Ratnam, Joseline
  • Gut, Jiri
  • Legac, Jennifer
  • Hansell, Elizabeth
  • Mackey, Zachary B
  • Skrzypczynska, Katarzyna M
  • Debnath, Anjan
  • Engel, Juan C
  • Rosenthal, Philip J
  • McKerrow, James H
  • Arkin, Michelle R
  • Renslo, Adam R
  • et al.
Abstract

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼ 2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View