期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 183, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111681
关键词
Malaria; Dihydroorotate dehydrogenase (DHODH) inhibitors; Leishmania; Trypanosoma; hDHODH; Antiviral; Pseudomonas aeruginosa; Aspergillus fumigatus; Toxoplasma gondii; Plasmodium falciparum; Plasmodium vivax; Helicobacter pilory; Babesia bovis; Theileria equi; Babesia caballi; Schistosoma mansoni; Brequinar; Leflunomide; Teriflunomide; Bioisosterism
资金
- University of Turin [LOLM_-RILO_17_01, LOLM_RILO_18_01, BOSD_RILO_17_01, BOS-D_RILO_18_01]
- Ministero degli Affari Esteri e della Cooperazione Internazionale [PGR00978]
Pyrimidines are essential for the cell survival and proliferation of living parasitic organisms, such as Helicobacter pylori, Plasmodium falciparum and Schistosoma mansoni, that are able to impact upon human health. Pyrimidine building blocks, in human cells, are synthesised via both de novo biosynthesis and salvage pathways, the latter of which is an effective way of recycling pre-existing nucleotides. As many parasitic organisms lack pyrimidine salvage pathways for pyrimidine nucleotides, blocking de novo biosynthesis is seen as an effective therapeutic means to selectively target the parasite without effecting the human host. Dihydroorotate dehydrogenase (DHODH), which is involved in the de novo biosynthesis of pyrimidines, is a validated target for anti-infective drug research. Recent advances in the DHODH microorganism field are discussed herein, as is the potential for the development of DHODH-targeted therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.
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