Zuma Aline Araujo, Teixeira de Macedo-Silva Sara, Achari Anushree, Vinayagam Jayaraman, Bhattacharjee Pinaki, Chatterjee Sourav, Gupta Vivek Kumar, Cristina de Sousa Leite Amanda, Souza de Castro Lucas, Jaisankar Parasuraman, de Souza Wanderley
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Cidade Universitária, Rio de Janeiro, CEP 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Av. Carlos Chagas Filho, 373, Cidade Universitária, Rio de Janeiro, CEP 21941-902, Brazil.
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700 032, India.
Exp Parasitol. 2021 May;224:108100. doi: 10.1016/j.exppara.2021.108100. Epub 2021 Mar 17.
Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.
恰加斯病和利什曼病是由锥虫科寄生虫引起的被忽视疾病,它们共同影响着五大洲数百万人。恰加斯病的治疗基于苯硝唑,而利什曼病可用的药物较少,如两性霉素B和米替福新。在这两种情况下,由于毒性或副作用,目前的治疗并不完全有效。受发现有效靶点和新治疗方案需求的鼓舞,我们评估了8种呋喃化合物对克氏锥虫和亚马逊利什曼原虫的作用,考虑了它们对增殖、感染和超微结构的影响。其中许多化合物能够损害克氏锥虫和亚马逊利什曼原虫的增殖,并引起超微结构改变,如高尔基体紊乱、自噬体形成和线粒体肿胀。综上所述,目前获得的结果使这些化合物有资格进入化疗研究的进一步阶段。