{"title":"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。","authors":"Pinky Gehlot, Vivek K Vyas","doi":"10.1080/13543776.2023.2280596","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Pyrimidine nucleotides are essential for the parasite's growth and replication. Parasites have only a <i>de novo</i> 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.</p><p><strong>Area covered: </strong>This review discussed the development of patented <i>Pf</i>DHODH inhibitors published between 2007 and 2023 along with their chemical structures and activities.</p><p><strong>Expert opinion: </strong><i>Pf</i>DHODH enzyme is involved in the rate-limiting fourth step of the pyrimidine biosynthesis pathway. Thus, inhibition of <i>Pf</i>DHODH 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 <i>Pf</i>DHODH inhibitors can be those newer agents. Many <i>Pf</i>DHODH inhibitors were patented in the past, and the dependency of <i>Plasmodium</i> on <i>de novo</i> pyrimidine provided a new approach for the development of novel antimalarial agents.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recent advances on patents of <i>Plasmodium falciparum</i> dihydroorotate dehydrogenase (<i>Pf</i>DHODH) inhibitors as antimalarial agents.\",\"authors\":\"Pinky Gehlot, Vivek K Vyas\",\"doi\":\"10.1080/13543776.2023.2280596\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Pyrimidine nucleotides are essential for the parasite's growth and replication. Parasites have only a <i>de novo</i> 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.</p><p><strong>Area covered: </strong>This review discussed the development of patented <i>Pf</i>DHODH inhibitors published between 2007 and 2023 along with their chemical structures and activities.</p><p><strong>Expert opinion: </strong><i>Pf</i>DHODH enzyme is involved in the rate-limiting fourth step of the pyrimidine biosynthesis pathway. Thus, inhibition of <i>Pf</i>DHODH 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 <i>Pf</i>DHODH inhibitors can be those newer agents. Many <i>Pf</i>DHODH inhibitors were patented in the past, and the dependency of <i>Plasmodium</i> on <i>de novo</i> pyrimidine provided a new approach for the development of novel antimalarial agents.</p>\",\"PeriodicalId\":12314,\"journal\":{\"name\":\"Expert Opinion on Therapeutic Patents\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Therapeutic Patents\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13543776.2023.2280596\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Therapeutic Patents","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543776.2023.2280596","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Recent advances on patents of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors as antimalarial agents.
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.
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
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