Barcelona Institute for Global Health (ISGlobal), Hospital Clinic-University of Barcelona, Barcelona 08036, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain.
Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martin 1109 O, San Juan, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290 (C1425FQB) CABA, Argentina.
Phytomedicine. 2022 Jul;101:154126. doi: 10.1016/j.phymed.2022.154126. Epub 2022 Apr 19.
Chagas disease, caused by the parasite Trypanosoma cruzi, affects over six million people worldwide, mainly in Latin American countries. Currently available drugs have variable efficacy in the chronic phase and significant side effects, so there is an urgent need for safer chemotherapeutic treatments. Natural products provide privileged structures that could serve as templates for the synthesis of new drugs. Among them, Amaryllidaceae plants have proved to be a potential natural source of therapeutical agents due to their rich diversity in alkaloids.
To identify alkaloids with anti-T. cruzi activity from Habranthus brachyandrus (Baker) Sealy (Amaryllidaceae, subfamily Amaryllidoideae) collected in Argentina.
An H. brachyandrus alkaloid extract was tested against T. cruzi, and its cytotoxicity profile was evaluated against two mammalian cell lines to ascertain its selectivity against the parasite and potential liver toxicity. It was also assessed by a stage-specific anti-amastigote assay and analysed by GC/MS to determine its alkaloid profile. The isolated alkaloids were also tested using the aforementioned assays.
The extract showed high and specific activity against T. cruzi. The alkaloids lycoramine, galanthindole, 8-O-demethylmaritidine, 8-O-demethylhomolycorine, nerinine, trisphaeridine, deoxytazettine, and tazettamide were identified by means of GC-MS. In addition, hippeastidine (also named aulicine), tazzetine, ismine, and 3-epimacronine were isolated. The alkaloid ismine was specifically active against the parasite and had low toxicity against HepG2 cells, but did not show anti-amastigote activity.
The extract had specific anti-T. cruzi activity and the isolated alkaloid ismine was partially responsible of it. These results encourage further exploration of H. brachyandrus alkaloids in search of novel starting points for Chagas disease drug development.
恰加斯病由寄生虫克氏锥虫引起，影响全球超过 600 万人，主要分布在拉丁美洲国家。目前可用的药物在慢性期疗效不一，且副作用明显，因此迫切需要更安全的化疗治疗方法。天然产物提供了有潜力的结构，可作为合成新药的模板。其中，石蒜科植物因其生物碱的丰富多样性而被证明是治疗药物的潜在天然来源。
从阿根廷采集的 Habranthus brachyandrus（Baker）Sealy（石蒜科，石蒜亚科）中鉴定具有抗 T. cruzi 活性的生物碱。
测试 H. brachyandrus 生物碱提取物对 T. cruzi 的活性，并评估其对两种哺乳动物细胞系的细胞毒性谱，以确定其对寄生虫的选择性和潜在的肝毒性。还通过阶段特异性抗变形体试验进行评估，并通过 GC/MS 分析确定其生物碱谱。还使用上述测定法测试分离的生物碱。
提取物对 T. cruzi 表现出高特异性和活性。通过 GC/MS 鉴定出了石蒜科生物碱-lycoramine、galanthindole、8-O-去甲马替丁、8-O-去甲 homolycorine、nerinine、trisphaeridine、脱氧 tazettine 和 tazettamide。此外，还分离出了 hippeastidine（也称为 aulicine）、tazzetine、isme 和 3-epimacronine。生物碱 ismine 对寄生虫具有特异性活性，对 HepG2 细胞的毒性较低，但对变形体无抗活性。
提取物具有特异性抗 T. cruzi 活性，分离的生物碱 ismine 部分对此活性负责。这些结果鼓励进一步探索 H. brachyandrus 生物碱，以寻找治疗恰加斯病的新药起点。
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