{"title":"探索疟原虫的新靶点及其潜在抑制剂,以对抗抗疟药物的抗药性。","authors":"Pratyusa Biswas, Rini Roy, Kuldip Ghosh, Debjani Nath, Asmita Samadder, Sisir Nandi","doi":"10.1007/s12639-024-01687-x","DOIUrl":null,"url":null,"abstract":"<p><p>Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. There is an acute need for novel antimalarial drugs that can put a stop to the future public health crisis caused by the multi-drug resistance strains of the <i>Plasmodium</i> parasite<i>.</i> However, the discovery of these new components is very challenging in the context of the generation of multi-drug resistance properties of malaria. The novel drugs also need to have several properties involving enhanced therapeutic prospects, successful treatment capabilities, and novel mechanisms of action that will forestall the resistance. To successfully achieve this aim researchers are trying to focus on exploring promising malaria targets. Various approaches have been made for the development of drugs for malaria including the remodelling of existing drugs and the development of novel inhibitors which acts on new targets. Advancement in the study provides more information on the biology of parasites and the new targets which help in the development of novel drugs. The present review focuses on the study of novel targets of malaria parasites and subsequent inhibitors of those particular targets. Some of these targets include malarial protease, various transporter proteins, enzymes involved in the synthesis of DNA, and nucleic acids like dihydroorotate dehydrogenase, dihydrofolate reductase, apicoplast and dihydropteroate synthase. Other potential targets are also included in this review such as isoprenoid biosynthesis, farnesyl transferase of parasite, <i>P. falciparum</i> translational elongation factor 2, and phosphatidyl inositol 4 kinase. These promising targets have also been summed up along with their corresponding inhibitors for combating multi-drug resistance malaria.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"48 4","pages":"671-722"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527868/pdf/","citationCount":"0","resultStr":"{\"title\":\"To quest new targets of <i>Plasmodium</i> parasite and their potential inhibitors to combat antimalarial drug resistance.\",\"authors\":\"Pratyusa Biswas, Rini Roy, Kuldip Ghosh, Debjani Nath, Asmita Samadder, Sisir Nandi\",\"doi\":\"10.1007/s12639-024-01687-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. 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引用次数: 0
摘要
疟疾仍然是一个全球性的健康挑战,每年都会造成大量死亡和发病,而寄生虫的抗药性菌株又使治疗工作复杂化。目前急需新型抗疟药物,以阻止疟原虫多重抗药性菌株造成的未来公共卫生危机。然而,在疟疾产生多重抗药性的背景下,发现这些新成分非常具有挑战性。新型药物还需要具备多种特性,包括增强的治疗前景、成功的治疗能力以及能够防止抗药性产生的新型作用机制。为了成功实现这一目标,研究人员正试图重点探索有前景的疟疾靶点。开发疟疾药物的方法多种多样,包括改造现有药物和开发作用于新靶点的新型抑制剂。研究的进展提供了更多关于寄生虫生物学和新靶点的信息,有助于新型药物的开发。本综述的重点是研究疟原虫的新靶点以及这些特定靶点的后续抑制剂。其中一些靶点包括疟原虫蛋白酶、各种转运蛋白、参与 DNA 和核酸合成的酶,如二氢烟酸脱氢酶、二氢叶酸还原酶、 apicoplast 和二氢蝶酸合成酶。本综述还包括其他潜在靶点,如异戊二烯生物合成、寄生虫的法尼基转移酶、恶性疟原虫翻译伸长因子 2 和磷脂酰肌醇 4 激酶。此外,还总结了这些有希望的靶点及其相应的抑制剂,以抗击多重抗药性疟疾。
To quest new targets of Plasmodium parasite and their potential inhibitors to combat antimalarial drug resistance.
Malaria remains a global health challenge with significant mortality and morbidity annually, with resistant parasite strains complicating treatment efforts. There is an acute need for novel antimalarial drugs that can put a stop to the future public health crisis caused by the multi-drug resistance strains of the Plasmodium parasite. However, the discovery of these new components is very challenging in the context of the generation of multi-drug resistance properties of malaria. The novel drugs also need to have several properties involving enhanced therapeutic prospects, successful treatment capabilities, and novel mechanisms of action that will forestall the resistance. To successfully achieve this aim researchers are trying to focus on exploring promising malaria targets. Various approaches have been made for the development of drugs for malaria including the remodelling of existing drugs and the development of novel inhibitors which acts on new targets. Advancement in the study provides more information on the biology of parasites and the new targets which help in the development of novel drugs. The present review focuses on the study of novel targets of malaria parasites and subsequent inhibitors of those particular targets. Some of these targets include malarial protease, various transporter proteins, enzymes involved in the synthesis of DNA, and nucleic acids like dihydroorotate dehydrogenase, dihydrofolate reductase, apicoplast and dihydropteroate synthase. Other potential targets are also included in this review such as isoprenoid biosynthesis, farnesyl transferase of parasite, P. falciparum translational elongation factor 2, and phosphatidyl inositol 4 kinase. These promising targets have also been summed up along with their corresponding inhibitors for combating multi-drug resistance malaria.
期刊介绍:
The primary constituency of the Journal of Parasitic Diseases is parasitology. It publishes original research papers (pure, applied and clinical), which contribute significantly to any area of parasitology. Research papers on various aspects of cellular and molecular parasitology are welcome.