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

    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

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