Title

Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites

Authors

Authors

M. P. Glenn; S. Y. Chang; C. Horney; K. Rivas; K. Yokoyama; E. E. Pusateri; S. Fletcher; C. G. Cummings; F. S. Buckner; P. R. Pendyala; D. Chakrabarti; S. M. Sebti; M. Gelb; W. C. Van Voorhis;A. D. Hamilton

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Med. Chem.

Keywords

PROTEIN FARNESYLTRANSFERASE; ANTIMALARIAL-DRUGS; FALCIPARUM; DISCOVERY; FARNESYL; CELLS; Chemistry, Medicinal

Abstract

Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC50 < 1 nM) and toxicity to cultured parasites at low concentrations (ED50 < 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.

Journal Title

Journal of Medicinal Chemistry

Volume

49

Issue/Number

19

Publication Date

1-1-2006

Document Type

Article

Language

English

First Page

5710

Last Page

5727

WOS Identifier

WOS:000240495600008

ISSN

0022-2623

Share

COinS