Abstract
Malaria is a devastating illness caused by multiple species of the Plasmodium genus. The parasite's falcipain proteases have been extensively studied as potential drug targets. Here we report the testing of two established cysteine protease inhibitor scaffolds against both chloroquine sensitive and chloroquine resistant parasites. A subset of purine derived nitriles killed the parasite with moderate potency, and these inhibitors do not seem to exert their antiproliferative effects as cysteine protease inhibitors. Compound potency was determined to be similar against both parasite strains, indicating a low probability of cross resistance with chloroquine. These compounds represent a novel antimalarial scaffold, and a potential starting point for the development new inhibitors.
| Original language | English |
|---|---|
| Pages (from-to) | 3546-3549 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 19 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 1 2009 |
Bibliographical note
Funding Information:This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI075517.
Funding
This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI075517.
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | |
| National Institute of Allergy and Infectious Diseases | U01AI075517 |
| St. Jude Children's Research Hospital | |
| American Lebanese Syrian Associated Charities |
Keywords
- Cysteine protease inhibitor
- Falcipain
- Malaria
- Purine nitrile
- Thiosemicarbazone
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
