Title

2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials

Authors

Authors

S. Olepu; P. K. Suryadevara; K. Rivas; K. Yokoyama; Clmj Verlinde; D. Chakrabarti; W. C. Van Voorhis;M. H. Gelb

Comments

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

Abbreviated Journal Title

Bioorg. Med. Chem. Lett.

Keywords

malaria; P. falciparum; anti-malarials; protein farnesyl-transferase; drug discovery; rational drug design; PRENYLATION; Chemistry, Medicinal; Chemistry, Organic

Abstract

A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

Journal Title

Bioorganic & Medicinal Chemistry Letters

Volume

18

Issue/Number

2

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

494

Last Page

497

WOS Identifier

WOS:000253410100008

ISSN

0960-894X

Share

COinS