Umehara Eric, Cajas Rayssa A, Conceição Gabriel B, Antar Guilherme M, Andricopulo Adriano D, Moraes Josué de, Lago João Henrique G
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André 09280-560, SP, Brazil.
Núcleo de Pesquisas em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, Brazil.
Molecules. 2025 Jan 11;30(2):267. doi: 10.3390/molecules30020267.
In the present study, the hexane extract from branches of (Winteraceae) displayed potent activity against parasites (100% mortality of the worms at 200 μg/mL). Bioactivity-guided fractionation afforded, in addition to the previously reported bioactive sesquiterpene 3,6-epidioxy-bisabola-1,10-diene, two chemically related drimane sesquiterpenes-polygodial () and 9-deoxymuzigadial (). The anti- effects for compounds and were determined in vitro, with compound demonstrating significant potency (EC value of 10 μM for both male and female worms), while was inactive. Cytotoxicity assays against Vero cells revealed no toxicity for either compound (CC > 200 μM). Additionally, an in silico analysis was conducted using the SwissADME platform for , revealing that this natural sesquiterpene exhibited adherence to several ADME parameters and no PAINS violations. Finally, in vivo studies with -infected mice treated with compound demonstrated a 44.0% reduction in worm burden, accompanied by decreases in egg production of 71.8% in feces and 69.5% in intestines. These findings highlight the potential of polygodial () as a promising prototype for schistosomiasis treatment.
在本研究中，来自（林仙科）树枝的己烷提取物对寄生虫显示出强效活性（在200μg/mL时蠕虫死亡率为100%）。生物活性导向的分离除了得到先前报道的具有生物活性的倍半萜3,6 - 环氧双环倍半萜 - 1,10 - 二烯外，还得到了两种化学相关的菖蒲烷倍半萜——多香木醛（）和9 - 脱氧穆氏醛（）。在体外测定了化合物和的抗作用，化合物显示出显著的效力（雄性和雌性蠕虫的EC值均为10μM），而无活性。针对Vero细胞的细胞毒性试验表明这两种化合物均无毒性（CC>200μM）。此外，使用SwissADME平台对进行了计算机分析，结果表明这种天然倍半萜符合几个ADME参数且不存在PAINS违规情况。最后，用化合物治疗感染的小鼠的体内研究表明，蠕虫负荷降低了44.0%，同时粪便中产卵量减少了71.8%，肠道中产卵量减少了69.5%。这些发现突出了多香木醛（）作为治疗血吸虫病的有前景的原型的潜力。
