González-Matos Maikel, Aguado Mirtha Elisa, Izquierdo Maikel, Monzote Lianet, González-Bacerio Jorge
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.
Exp Parasitol. 2024 May;260:108747. doi: 10.1016/j.exppara.2024.108747. Epub 2024 Mar 20.
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.
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。