Dereplication Study by HPLC-MS-MS and activity against Leishmania chagasi of the leaf extract of Trichilia emarginata

The leaves extract of T. emarginata was evaluated for its activity against Leishmania chagasi and was studied by dereplication by HPLC-DAD-MS/MS analysis supported by the Global Natural Products and Social Molecular Networking (GNPS) platform1. The search for the chemical constituents of the crude extract and its fractions ethyl acetate (EAF) and hydroalcoholic (HAF) of de T. emarginata led to the identification of 5-O-caffeoylquinic acid (5-CQA), a substance already described in the Trichilia genus2.However, other metabolites were identified for the first time in this genus, including the isomers 3 and 4-O-caffeoylquinic acids, aside from p-coumaroylquinic acid, di-O-caffeoylquinic acid and caffeoyl-dimethoxycinnamoylquinic acid. Due to the abundance of these acid metabolites in all samples of T. emarginata, it is believed to have a close relation with the leishmanicidal activity observed in the assays with L. chagasi. In addition, some flavonoids derived from quercetin and taxifolin were also identified. Among all tested samples, HAF showed to be the most potent with an IC50 of 11.40 μg/m and its chromatographic profile showed that 5-CQA and its derivatives are the major constituents. The commercial 5-CQA was tested and showed higher leishmanicidal activity than HAF against L. chagasi (IC50 = 7.38 μg/mL). In conclusion, our results strongly suggest that the leishmanicidal activity of HAF of T. emarginata is mainly due to the presence of 5-CQA and, possibly, of its other derivatives. The GNPS platform was of great value in the dereplication study, allowing for the identification of known metabolites.