DA Silva Cristiane França, Daliry Anissa, DA Silva Patrícia Bernardino, Akay Senol, Banerjee Moloy, Farahat Abdelbasset A, Fisher Mary K, Hu Laixing, Kumar Arvind, Liu Zongying, Stephens Chad E, Boykin David W, Correia Soeiro Maria D E Nazaré
Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil.
Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
Parasitology. 2011 Dec;138(14):1863-9. doi: 10.1017/S0031182011001429. Epub 2011 Sep 9.
The present study aimed to determine the in vitro biological efficacy and selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular amastigotes of Trypanosoma cruzi. The biological activity of these aromatic compounds was assayed for 48 and 24 h against intracellular parasites and bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were also performed to determine their potential use in blood banks by treating the bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4°C. Toxicity against mammalian cells was evaluated using primary cultures of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death rates were determined by MTT colorimetric assays. Our data demonstrated the outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853, DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar against both parasite forms. All AIAs presented superior efficacy to benznidazole and some, such as DB1868, also demonstrated promising activity as a candidate agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these novel AIAs against T. cruzi stimulates further in vivo studies and justifies the screening of new analogues with the goal of establishing a useful alternative therapy for Chagas disease.
本研究旨在确定7种新型芳香族咪唑类化合物（AIAs）对克氏锥虫血流型锥鞭毛体和细胞内无鞭毛体的体外生物学疗效和选择性。分别在48小时和24小时内测定了这些芳香族化合物对克氏锥虫（Y株）细胞内寄生虫和血流型的生物学活性。还进行了额外的试验，通过在4°C下用稀释于小鼠血液中的化合物处理血流型寄生虫24小时，来确定它们在血库中的潜在用途。使用原代培养的心肌细胞评估对哺乳动物细胞的毒性，将心肌细胞与AIAs一起孵育24小时和48小时，然后通过MTT比色法测定细胞死亡率。我们的数据表明，AIAs对克氏锥虫具有显著的杀锥虫作用，尤其是DB1853、DB1862、DB1867和DB1868，对两种寄生虫形式的IC50值在16至70纳摩尔之间。所有AIAs的疗效均优于苯硝唑，一些化合物，如DB1868，作为血液预防候选药物也显示出有前景的活性。这些新型AIAs对克氏锥虫的优异抗锥虫疗效刺激了进一步的体内研究，并证明有必要筛选新的类似物，以期为恰加斯病建立一种有效的替代疗法。
