de Oliveira Filho Virlânio A, Gubiani Juliana R, Borgonovi Vitória D, Hilário Felipe, de Amorim Marcelo R, Minori Karen, Bertolini Vitor K S, Ferreira Antonio G, Biz Andressa R, Soares Marcos A, Teles Helder L, Gadelha Fernanda R, Berlinck Roberto G S, Miguel Danilo C
Instituto de Biologia, Universidade Estadual de Campinas, Campinas 13083-862, SP, Brazil.
Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, 13560-970 São Carlos, SP, Brazil.
J Nat Prod. 2024 Dec 27;87(12):2829-2838. doi: 10.1021/acs.jnatprod.4c01098. Epub 2024 Dec 3.
Leishmaniasis is a worldwide disease caused by more than 20 species of parasites. and are among the main causative agents of cutaneous leishmaniasis, presenting a broad spectrum of clinical forms. As these pathologies lead to unsatisfactory treatment outcomes, the discovery of alternative chemotherapeutic options is urgently required. In this investigation, a leishmanicidal bioassay-guided fractionation of the growth media extract produced by P63 led to the isolation of the cyclic depsipeptide beauvericin (). The viability of , and mammalian cells (macrophages and L929 fibroblasts) was assessed in incubated cultures. promastigotes were sensitive to , with EC values ranging from 0.7 to 1.3 μM. Microscopy analysis indicated that spp. parasites showed morphological abnormalities in a dose-dependent manner in the presence of . intracellular amastigotes were more sensitive to than promastigotes (EC = 0.8 ± 0.1 μM), with a good selectivity index (22-30). reduced the infectivity index at very low concentrations, maintaining the integrity of the primary murine host cell for up to the highest concentration tested for . assays of conducted using BALB/c mice infected with stationary-phase promastigotes of in the tail base presented a significant reduction in the lesion parasite load. A second round of assays was performed to assess the efficacy of the topical use of . The results demonstrated a significant decrease in the total ulcerated area of mice treated with when compared with untreated animals. Our results present promising and leishmanicidal effects of beauvericin, emphasizing that systemic inoculation of led to a decrease in the parasite load at the lesion site, whereas topical administration of delayed the progression of leishmaniasis ulcers, a cure criterion established for cutaneous leishmaniasis management.
利什曼病是一种由20多种寄生虫引起的全球性疾病。[具体寄生虫名称1]和[具体寄生虫名称2]是皮肤利什曼病的主要病原体，呈现出广泛的临床形式。由于这些病症导致治疗效果不理想，迫切需要发现替代的化疗方案。在本研究中，对由P63产生的生长培养基提取物进行利什曼原虫杀伤生物测定指导的分级分离，导致环状缩肽白僵菌素（[具体化学式]）的分离。在[具体培养条件]培养的细胞中评估了[具体寄生虫名称1]、[具体寄生虫名称2]和哺乳动物细胞（巨噬细胞和L929成纤维细胞）的活力。[具体寄生虫名称1]前鞭毛体对[白僵菌素]敏感，EC值范围为0.7至1.3μM。显微镜分析表明，在[白僵菌素]存在下，[具体寄生虫名称1]属寄生虫呈剂量依赖性地表现出形态异常。细胞内无鞭毛体比前鞭毛体对[白僵菌素]更敏感（EC = 0.8±0.1μM），具有良好的选择性指数（22 - 30）。[白僵菌素]在非常低的浓度下降低了感染指数，在测试的最高浓度下，原代小鼠宿主细胞的完整性得以维持。使用感染了尾基部静止期前鞭毛体的[具体寄生虫名称1]的BALB/c小鼠进行的[白僵菌素]试验表明，病变部位的寄生虫负荷显著降低。进行了第二轮[白僵菌素]试验以评估局部使用[白僵菌素]的疗效。结果表明，与未治疗的动物相比，用[白僵菌素]治疗的小鼠的总溃疡面积显著减少。我们的结果显示了白僵菌素对[具体寄生虫名称1]和[具体寄生虫名称2]有有前景的杀伤利什曼原虫的作用，强调全身接种[白僵菌素]导致病变部位的寄生虫负荷降低，而局部施用[白僵菌素]延缓了利什曼病溃疡的进展，这是皮肤利什曼病管理确立的治愈标准。
