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探寻疟原虫的新靶点及其对抗疟药耐药性的潜在抑制剂。

To quest new targets of parasite and their potential inhibitors to combat antimalarial drug resistance.

作者信息

Biswas Pratyusa, Roy Rini, Ghosh Kuldip, Nath Debjani, Samadder Asmita, Nandi Sisir

机构信息

Department of Zoology, University of Kalyani, Kalyani, Nadia 741235 India.

Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research (Affiliated to Veer Madho Singh Bhandari Uttarakhand Technical University), Kashipur, 244713 India.

出版信息

J Parasit Dis. 2024 Dec;48(4):671-722. doi: 10.1007/s12639-024-01687-x. Epub 2024 May 31.

Abstract

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 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, 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.

摘要

疟疾仍然是一项全球性的健康挑战,每年都有大量的死亡率和发病率,耐药寄生虫菌株使治疗工作变得复杂。迫切需要能够阻止由该寄生虫的多药耐药菌株引发的未来公共卫生危机的新型抗疟药物。然而,在疟疾产生多药耐药特性的背景下,发现这些新成分极具挑战性。新型药物还需要具备多种特性,包括增强治疗前景、成功的治疗能力以及能够防止耐药性的新作用机制。为了成功实现这一目标,研究人员正致力于探索有前景的疟疾靶点。已经采取了各种方法来开发抗疟药物,包括对现有药物进行改造以及开发作用于新靶点的新型抑制剂。该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,这有助于新型药物的开发。本综述重点关注疟原虫新靶点的研究以及这些特定靶点的后续抑制剂。其中一些靶点包括疟疾蛋白酶、各种转运蛋白、参与DNA合成的酶以及核酸,如二氢乳清酸脱氢酶、二氢叶酸还原酶、质体和二氢蝶酸合酶。本综述还包括其他潜在靶点,如类异戊二烯生物合成、寄生虫的法尼基转移酶、翻译延伸因子2和磷脂酰肌醇4激酶。这些有前景的靶点及其相应的抑制剂也被总结出来,用于对抗多药耐药疟疾。

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