Chemical Constituents and Cytotoxic Activity of Rhinella jimi (Anura: Bufonidae)

Abstract

Rhinella jimi toads (Stevaux, 2002) belong to the Bufonidae family, are endemic in the Brazilian Northeast and are commonly found during rainy periods. In general, amphibians of this family have in their poisons different metabolites that show a diversity of pharmacological activities. The isolation and identification of these compounds are of great importance, and techniques such as high-performance liquid chromatography coupled to mass spectrometry are widely used for the discovery of novel and known compounds in these poisons. For R. jimi poison, the ethyl acetate and methanolic extracts were obtained and thirty compounds were identified by combining ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) with direct infusion atmospheric pressure chemical ionization mass spectrometry (DI-APCI-MS/MS) and direct infusion electrospray mass spectrometry (DI-ESI-MS/MS) for each extract, respectively. Marinobufagin (2) and marinobufotoxin (19) were the majorities of each extract, respectively. In addition, other bufadienolides mainly present in the ethyl acetate extract, such other bufotoxins, alkaloids and arginine diacid derivatives were identified in the methanol extract. In a cytotoxic assay by 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide (MTT), the extracts and compound 2 demonstrated half-maximal inhibitory concentration (IC50) values better than the positive control doxorubicin, evidencing excellent cytotoxic. This is the most complete study of the chemical composition of R. jimi toad poison and its respective cytotoxic activity, promoting the enrichment of knowledge about this family and species.