A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment.
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Nov 1 2020|
Bibliographical noteFunding Information:
This work was supported by the Center for Applied Biotechnology at California Polytechnic State University, the Bill and Linda Frost Fund and Grand Challenges Canada .
© 2020 Elsevier Ltd
- Plasmodium falciparum
- Structure activity relationship
- Structure based design
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry