Recent advances on patents of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors as antimalarial agents.

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Expert Opinion on Therapeutic Patents Pub Date : 2023-07-01 Epub Date: 2023-11-28 DOI:10.1080/13543776.2023.2280596
Pinky Gehlot, Vivek K Vyas
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Abstract

Introduction: Pyrimidine nucleotides are essential for the parasite's growth and replication. Parasites have only a de novo pathway for the biosynthesis of pyrimidine nucleotides. Dihydroorotate dehydrogenase (DHODH) enzyme is involved in the rate-limiting step of the pyrimidine biosynthesis pathway. DHODH is a biochemical target for the discovery of new antimalarial agents.

Area covered: This review discussed the development of patented PfDHODH inhibitors published between 2007 and 2023 along with their chemical structures and activities.

Expert opinion: PfDHODH enzyme is involved in the rate-limiting fourth step of the pyrimidine biosynthesis pathway. Thus, inhibition of PfDHODH using species-selective inhibitors has drawn much attention for treating malaria because they inhibit parasite growth without affecting normal human functions. Looking at the current scenario of antimalarial drug resistance with most of the available antimalarial drugs, there is a huge need for targeted newer agents. Newer agents with unique mechanisms of action may be devoid of drug toxicity, adverse effects, and the ability of parasites to quickly gain resistance, and PfDHODH inhibitors can be those newer agents. Many PfDHODH inhibitors were patented in the past, and the dependency of Plasmodium on de novo pyrimidine provided a new approach for the development of novel antimalarial agents.

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恶性疟原虫二氢乳清酸脱氢酶(PfDHODH)抑制剂作为抗疟药物专利的最新进展。
引言:嘧啶核苷酸对寄生虫的生长和复制至关重要。寄生虫只有嘧啶核苷酸生物合成的从头途径。二氢乳清酸脱氢酶(DHODH)参与嘧啶生物合成途径的限速步骤。DHODH是发现新的抗疟药物的生化靶点。涵盖领域:本综述讨论了2007年至2023年间发表的PfDHODH专利抑制剂的开发及其化学结构和活性。专家意见:PfDHODH酶参与嘧啶生物合成途径的限速第4步。因此,使用物种选择性抑制剂抑制PfDHODH在治疗疟疾方面引起了广泛关注,因为它们在不影响正常人体功能的情况下抑制寄生虫生长。从目前大多数可用抗疟药物的抗疟耐药性来看,对靶向新药物的需求巨大。具有独特作用机制的新型药物可能没有药物毒性、副作用和寄生虫快速获得耐药性的能力,而PfDHODH抑制剂可能就是这些新型药物。许多PfDHODH抑制剂过去都获得了专利,疟原虫对从头嘧啶的依赖性为开发新型抗疟药物提供了新的途径。
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来源期刊
CiteScore
12.10
自引率
1.50%
发文量
50
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Therapeutic Patents (ISSN 1354-3776 [print], 1744-7674 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on recent pharmaceutical patent claims, providing expert opinion the scope for future development, in the context of the scientific literature. The Editors welcome: Reviews covering recent patent claims on compounds or applications with therapeutic potential, including biotherapeutics and small-molecule agents with specific molecular targets; and patenting trends in a particular therapeutic area Patent Evaluations examining the aims and chemical and biological claims of individual patents Perspectives on issues relating to intellectual property The audience consists of scientists, managers and decision-makers in the pharmaceutical industry and others closely involved in R&D Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days.
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