دورية أكاديمية
A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 1: triazolopyrimidine, isoxazolopyrimidine and pyrrole-based (DSM) compounds.
| العنوان: | A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 1: triazolopyrimidine, isoxazolopyrimidine and pyrrole-based (DSM) compounds. |
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| المؤلفون: | Sharma M; Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India., Pandey V; MIT College of Pharmacy, Ramganga Vihar, Phase-II, Moradabad, UP-244001, India., Poli G; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy., Tuccinardi T; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy., Lolli ML; Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10125 - Turin, Italy., Vyas VK; Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India. Electronic address: vivekvyas@nirmauni.ac.in. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2024 May; Vol. 146, pp. 107249. Date of Electronic Publication: 2024 Mar 03. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| مواضيع طبية MeSH: | Antimalarials*/chemistry , Oxidoreductases Acting on CH-CH Group Donors*/chemistry, Plasmodium falciparum ; Pyrroles/pharmacology ; Dihydroorotate Dehydrogenase ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/chemistry |
| مستخلص: | One of the deadliest infectious diseases, malaria, still has a significant impact on global morbidity and mortality. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the fourth step in de novo pyrimidine nucleotide biosynthesis and has been clinically validated as an innovative and promising target for the development of novel targeted antimalarial drugs. PfDHODH inhibitors have the potential to significantly slow down parasite growth at the blood and liver stages. Several PfDHODH inhibitors based on various scaffolds have been explored over the past two decades. Among them, triazolopyrimidines, isoxazolopyrimidines, and pyrrole-based derivatives known as DSM compounds showed tremendous potential as novel antimalarial agents, and one of the triazolopyrimidine-based compounds (DSM265) was able to reach phase IIa clinical trials. DSM compounds were synthesized as PfDHODH inhibitors with various substitutions based on structure-guided medicinal chemistry approaches and further optimised as well. For the first time, this review provides an overview of all the synthetic approaches used for the synthesis, alternative synthetic routes, and novel strategies involving various catalysts and chemical reagents that have been used to synthesize DSM compounds. We have also summarized SAR study of all these PfDHODH inhibitors. In an attempt to assist readers, scientists, and researchers involved in the development of new PfDHODH inhibitors as antimalarials, this review provides accessibility of all synthetic techniques and SAR studies of the most promising triazolopyrimidines, isoxazolopyrimidines, and pyrrole-based PfDHODH inhibitors. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antimalarial agents; PfDHODH inhibitors; Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH); Structure-activity relationship (SAR); Synthesis; Triazolopyrimidines |
| المشرفين على المادة: | 0 (Antimalarials) EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors) 0 (Pyrroles) 0 (Dihydroorotate Dehydrogenase) 0 (Enzyme Inhibitors) |
| تواريخ الأحداث: | Date Created: 20240317 Date Completed: 20240415 Latest Revision: 20240415 |
| رمز التحديث: | 20240415 |
| DOI: | 10.1016/j.bioorg.2024.107249 |
| PMID: | 38493638 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2024.107249 |