Squalestatin is an inhibitor of carotenoid biosynthesis in Plasmodium falciparum

Antimicrobial Agents and Chemotherapy
Heloisa B GabrielMauro F Azevedo

Abstract

The increasing resistance of malaria parasites to almost all available drugs calls for the characterization of novel targets and the identification of new compounds. Carotenoids are polyisoprenoids from plants, algae, and some bacteria, and they are biosynthesized by Plasmodium falciparum but not by mammalian cells. Biochemical and reverse genetics approaches were applied to demonstrate that phytoene synthase (PSY) is a key enzyme for carotenoid biosynthesis in P. falciparum and is essential for intraerythrocytic growth. The known PSY inhibitor squalestatin reduces biosynthesis of phytoene and kills parasites during the intraerythrocytic cycle. PSY-overexpressing parasites showed increased biosynthesis of phytoene and its derived product phytofluene and presented a squalestatin-resistant phenotype, suggesting that this enzyme is the primary target of action of this drug in the parasite.

References

Dec 1, 1979·Antimicrobial Agents and Chemotherapy·R E DesjardinsJ D Chulay
Aug 20, 1976·Science·W Trager, J B Jensen
Feb 1, 1990·Nature·J L Goldstein, M S Brown
Oct 1, 1983·Biochemical Society Transactions·T W Goodwin
Jul 15, 1993·European Journal of Biochemistry·H Sies
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·Y WuT E Wellems
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J D BergstromO D Hensens
Mar 1, 1997·Experimental Physiology·H Sies
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·D A Fidock, T E Wellems
Jun 22, 1999·Molecular and Biochemical Parasitology·T F de Koning-WardC J Janse
Aug 15, 2001·Antimicrobial Agents and Chemotherapy·I C MouraE A Kimura
Aug 27, 2002·The Journal of Biological Chemistry·Debopam ChakrabartiCharles M Allen
Sep 27, 2002·Chembiochem : a European Journal of Chemical Biology·Gerhard Sandmann
Feb 22, 2003·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·John C GrayDaniel MacLean
Jun 18, 2003·Experimental Parasitology·Carmen Fernandez-BecerraHernando A del Portillo
Jul 12, 2003·Trends in Parasitology·Sylke MüllerR Luise Krauth-Siegel
Dec 10, 2003·Current Opinion in Biotechnology·Benjamin N Mijts, Claudia Schmidt-Dannert
Mar 12, 2004·Annual Review of Plant Physiology and Plant Molecular Biology·F. X. Cunningham, E. Gantt
Mar 24, 2004·International Journal for Parasitology·Katja BeckerHagai Ginsburg
Jun 16, 2004·Cellular and Molecular Life Sciences : CMLS·W EisenreichF Rohdich
Sep 29, 2004·The Journal of Biological Chemistry·María B CasseraAlejandro M Katzin
Oct 13, 2004·The Journal of Infectious Diseases·Steffen BorrmannPeter G Kremsner
Oct 16, 2004·Molecular and Biochemical Parasitology·Paula L HawthorneDonald L Gardiner
Jun 14, 2005·Biochimica Et Biophysica Acta·Wiesław I Gruszecki, Kazimierz Strzałka
May 29, 2007·Journal of Agricultural and Food Chemistry·Veridiana V de Rosso, Adriana Z Mercadante
Nov 4, 2008·Trends in Parasitology·Tania F de Koning-Ward, Paul R Gilson
Feb 11, 2009·The Journal of Biological Chemistry·Renata TonhosoloAlejandro M Katzin
Jun 30, 2009·The Journal of Biological Chemistry·Hayley E BullenPaul R Gilson
Dec 25, 2010·The Journal of Biological Chemistry·Micha A HaeuptleThierry Hennet
Apr 5, 2013·Clinical Microbiology Reviews·Balbir Singh, Cyrus Daneshvar
Jul 30, 2014·The Journal of Physical Chemistry. B·Ana MartínezAntonio J Meléndez-Martínez

❮ Previous
Next ❯

Citations

Nov 9, 2018·Frontiers in Pharmacology·Bee Ling TanHeshu Sulaiman Rahman
May 12, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bee Ling Tan, Mohd Esa Norhaizan
Oct 5, 2017·Biochemistry·Jack G GanleyEmily R Derbyshire

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.