Plasmodium falciparum dihydroorotate dehydrogenase: a drug target against malaria

Future Medicinal Chemistry
Lucas Vb HoelzNubia Boechat

Abstract

Malaria remains one of the most lethal infectious diseases worldwide, and the most severe form is caused by Plasmodium falciparum. In recent decades, the major challenge to treatment of this disease has been the ability of the protozoan parasite to develop resistance to the drugs that are currently in use. Among P. falciparum enzymes, P. falciparum dihydroorotate dehydrogenase has been identified as an important target in drug discovery. Interference with the activity of this enzyme inhibits de novo pyrimidine biosynthesis and consequently prevents malarial infection. Organic synthesis, x-ray crystallography, high-throughput screening and molecular modeling methods such as molecular docking, quantitative structure-activity relationships, structure-based pharmacophore mapping and molecular dynamics simulations have been applied to the discovery of new inhibitors of P. falciparum dihydroorotate dehydrogenase.

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Citations

Apr 6, 2019·Metabolomics : Official Journal of the Metabolomic Society·Lucas A ChibliFernando B Da Costa
Apr 5, 2020·Marine Drugs·María Álvarez-BardónRafael Balaña-Fouce
Sep 2, 2020·Biochemical Society Transactions·Petar P S CalicSheena McGowan
Nov 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luiz C S PinheiroNubia Boechat
Sep 27, 2019·European Journal of Medicinal Chemistry·Donatella BoschiMarco L Lolli
Dec 10, 2020·Current Topics in Medicinal Chemistry·Vladimir B SulimovAlexey V Sulimov

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Methods Mentioned

BETA
glycosylation
Nuclear Magnetic Resonance

Software Mentioned

MOE
SPROUT
GOLD
PYMOL
Discovery
CoMFA CoMSIA
Autodock
CoMFA
eHITS
CoMSIA

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