Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile.
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile.
J Ethnopharmacol. 2014 Sep 11;155(2):1076-85. doi: 10.1016/j.jep.2014.06.025. Epub 2014 Jun 16.
Toads known as "cururú" (Rhinella schneideri) have been used in the Brazilian Pantanal and Paraguayan Chaco wetlands to treat erysipelas and cancer. The aim of the study was to assess the antiproliferative effect of the venom obtained from Rhinella schneideri and to identify its constituents by spectroscopic and spectrometric methods.
The venom was obtained by gentle pressing the parotid glands of the toads. The dry crude drug was analyzed by HPLC-MS-MS and chromatographed on Sephadex LH-20 to obtain purified compounds and fractions for spectroscopic analysis. The venom and fractions were evaluated for antiproliferative activity towards normal human lung fibroblasts (MRC-5) and four human cancer cell lines: gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1), bladder carcinoma (J82) and promyelocytic leukemia (HL-60).
From the Rhinella schneideri venom, 29 compounds were isolated and/or identified by spectroscopic and spectrometric means. Three known alkaloids and five argininyl diacids were identified in the complex mixture by HPLC-MS-MS. Nine out of fifteen argininyl diacid derivatives of the bufadienolides bufalin, marinobufagin and telocinobufagin are reported for the first time and four argininyl diacids are described for the first time as natural products. The venom and the fractions 9-13 showed a remarkable antiproliferative effect, with IC50 values in the range 0.019-0.022, 0.035-0.040, 0.028-0.064, 0.042-0.056 and 0.044-0.052 µg/mL for MRC-5, AGS, SK-MES-1, J82 and HL-60 cell lines, respectively. Under the same experimental conditions, IC50 values of the reference compound etoposide were 2.296, 0.277, 1.295, 1.884 and 1.059 µg/mL towards MRC-5, AGS, SK-MES-1, J82 and HL-60 cells, respectively.
The venom showed a strong antiproliferative effect towards human cancer cells and presented a high chemical diversity in its constituents, supporting its use as anticancer agent. These findings encourage further work on the chemistry and bioactivity of South American toad venoms.
在巴西潘塔纳尔和巴拉圭查科湿地，被称为“cururú”的蟾蜍（Rhinella schneideri）被用于治疗丹毒和癌症。本研究的目的是评估从 Rhinella schneideri 获得的毒液的抗增殖作用，并通过光谱和光谱方法鉴定其成分。
通过轻轻按压蟾蜍的腮腺获得毒液。通过 HPLC-MS-MS 分析干燥的粗提物，并在 Sephadex LH-20 上进行色谱分离，以获得用于光谱分析的纯化化合物和馏分。评估毒液和馏分对正常人类肺成纤维细胞（MRC-5）和四种人类癌细胞系：胃上皮腺癌（AGS）、肺癌（SK-MES-1）、膀胱癌（J82）和早幼粒细胞白血病（HL-60）的增殖活性。
从 Rhinella schneideri 毒液中分离出 29 种化合物，并通过光谱和光谱方法鉴定。通过 HPLC-MS-MS 在复杂混合物中鉴定出三种已知生物碱和五种精氨酰二羧酸。Bufalin、marinobufagin 和 telocinobufagin 的 15 个精氨酰二羧酸衍生物中有 9 个为首次报道，4 个精氨酰二羧酸为首次报道为天然产物。毒液和馏分 9-13 对 MRC-5、AGS、SK-MES-1、J82 和 HL-60 细胞系表现出显著的抗增殖作用，IC50 值分别为 0.019-0.022、0.035-0.040、0.028-0.064、0.042-0.056 和 0.044-0.052µg/mL。在相同的实验条件下，参考化合物依托泊苷对 MRC-5、AGS、SK-MES-1、J82 和 HL-60 细胞的 IC50 值分别为 2.296、0.277、1.295、1.884 和 1.059µg/mL。
毒液对人类癌细胞表现出强烈的抗增殖作用，并在其成分中表现出很高的化学多样性，支持将其用作抗癌剂。这些发现鼓励进一步研究南美蟾蜍毒液的化学和生物活性。
