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在临床前水平上具有作为利什曼病新型化疗药物潜力的化合物。

Compounds with potentialities as novel chemotherapeutic agents in leishmaniasis at preclinical level.

作者信息

González-Matos Maikel, Aguado Mirtha Elisa, Izquierdo Maikel, Monzote Lianet, González-Bacerio Jorge

机构信息

Center for Protein Studies, Faculty of Biology, University of Havana, Calle 25 #455 Entre I y J, Vedado, La Habana, Cuba.

Department of Parasitology, Center for Research, Diagnosis and Reference, Tropical Medicine Institute "Pedro Kourí", Autopista Novia Del Mediodía Km 6½, La Lisa, La Habana, Cuba.

出版信息

Exp Parasitol. 2024 May;260:108747. doi: 10.1016/j.exppara.2024.108747. Epub 2024 Mar 20.

DOI:10.1016/j.exppara.2024.108747
PMID:38518969
Abstract

Leishmaniasis are neglected infectious diseases caused by kinetoplastid protozoan parasites from the genus Leishmania. These sicknesses are present mainly in tropical regions and almost 1 million new cases are reported each year. The absence of vaccines, as well as the high cost, toxicity or resistance to the current drugs determines the necessity of new treatments against these pathologies. In this review, several compounds with potentialities as new antileishmanial drugs are presented. The discussion is restricted to the preclinical level and molecules are organized according to their chemical nature, source and molecular targets. In this manner, we present antimicrobial peptides, flavonoids, withanolides, 8-aminoquinolines, compounds from Leish-Box, pyrazolopyrimidines, and inhibitors of tubulin polymerization/depolymerization, topoisomerase IB, proteases, pteridine reductase, N-myristoyltransferase, as well as enzymes involved in polyamine metabolism, response against oxidative stress, signaling pathways, and sterol biosynthesis. This work is a contribution to the general knowledge of these compounds as antileishmanial agents.

摘要

利什曼病是由利什曼原虫属的动质体原生动物寄生虫引起的被忽视的传染病。这些疾病主要存在于热带地区,每年报告的新病例近100万例。由于缺乏疫苗,以及现有药物成本高、毒性大或存在耐药性,因此有必要研发针对这些病症的新疗法。在本综述中,介绍了几种具有作为新型抗利什曼病药物潜力的化合物。讨论仅限于临床前水平,分子根据其化学性质、来源和分子靶点进行分类。通过这种方式,我们介绍了抗菌肽、黄酮类化合物、睡茄内酯、8-氨基喹啉、来自Leish-Box的化合物、吡唑并嘧啶,以及微管蛋白聚合/解聚抑制剂、拓扑异构酶IB、蛋白酶、蝶啶还原酶、N-肉豆蔻酰转移酶,以及参与多胺代谢、抗氧化应激反应、信号通路和甾醇生物合成的酶。这项工作有助于增进对这些化合物作为抗利什曼病药物的一般认识。

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1
Compounds with potentialities as novel chemotherapeutic agents in leishmaniasis at preclinical level.在临床前水平上具有作为利什曼病新型化疗药物潜力的化合物。
Exp Parasitol. 2024 May;260:108747. doi: 10.1016/j.exppara.2024.108747. Epub 2024 Mar 20.
2
Promising therapeutic targets for antileishmanial drugs.抗利什曼原虫药物的潜在治疗靶点。
Expert Opin Ther Targets. 2002 Aug;6(4):407-22. doi: 10.1517/14728222.6.4.407.
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Mechanisms of drug action and drug resistance in Leishmania as basis for therapeutic target identification and design of antileishmanial modulators.利什曼原虫的药物作用机制和耐药性作为治疗靶点识别及抗利什曼原虫调节剂设计的基础
Curr Top Med Chem. 2006;6(5):539-50. doi: 10.2174/156802606776743165.
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Antimicrobial peptides for leishmaniasis.用于治疗利什曼病的抗菌肽。
Curr Opin Investig Drugs. 2010 Aug;11(8):868-75.
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Targeting pteridine reductase 1 and dihydrofolate reductase: the old is a new trend for leishmaniasis drug discovery.靶向蝶呤还原酶 1 和二氢叶酸还原酶:旧的方法成为利什曼病药物发现的新趋势。
Future Med Chem. 2019 Aug;11(16):2107-2130. doi: 10.4155/fmc-2018-0512. Epub 2019 Aug 2.
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Unveiling the Targets Involved in the Quest of Antileishmanial Leads Using In silico Methods.运用计算机方法揭示抗利什曼病先导化合物的作用靶点。
Curr Drug Targets. 2020;21(7):681-712. doi: 10.2174/1389450121666200128112948.
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Promising Molecular Targets Related to Polyamine Biosynthesis in Drug Discovery against Leishmaniasis.在抗利什曼病药物研发中与多胺生物合成相关的有前景的分子靶点
Med Chem. 2022;19(1):2-9. doi: 10.2174/1573406418666220713145446.
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The chemotherapeutic potential of chalcones against leishmaniases: a review.查耳酮类化合物在抗利什曼病方面的化疗潜力:综述。
Int J Antimicrob Agents. 2018 Mar;51(3):311-318. doi: 10.1016/j.ijantimicag.2017.06.010. Epub 2017 Jun 28.
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Modes of action of Leishmanicidal antimicrobial peptides.抗利什曼原虫抗菌肽的作用模式。
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Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa.关于抗菌肽 temporin A、B 和 1Sa 的抗利什曼原虫特性的研究。
J Pept Sci. 2011 Nov;17(11):751-5. doi: 10.1002/psc.1398. Epub 2011 Aug 1.

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