Estudo fitoquímico e investigação da atividade citotóxica das cascas do caule de Duguetia surinamensis (Annonaceae)

Abstract

Duguetia surinamensis R. E. Fries is a species of Annonaceae endemic to the Amazon, and can be found in Brazil, Colombia and Guianas. According to the literature, there are no reports of chemical and pharmacological studies about it. In this work, the phytochemical and in vitro cytotoxicity studies of the crude extracts and fractions of the stem of D. surinamensis were carried out, which led to the isolation of nine substances, eight of them of the alkaloid class. For this, classical chromatographic techniques were used for the isolation of the chemical constituents, and spectroscopic techniques (NMR 1H and 13C 1D/2D) and spectrometric (MS) for the identification of these constituents. The alkaloids isolated were identified as belonging to the subclasses of aporphines (duguetine, duguetine N-oxide, dicentrine and 7-hydroxynordicentrine), oxoaporphines (dicentrinone), tetrahydroprotoberberines (tetrahydrojathrorrizine), morphinanodienone (pallidine), and an alkaloid with a novel isoquinoline skeleton. The ninth isolated substance was benzene 1,2,4-trimethoxybenzene. Of these substances, only the alkaloids tetrahydrojathrorrizine, duguetine, duguetine N-oxide and dicentrinone are reported in the genus. 7-hydroxyncedicentrin was isolated for the first time in the family. The methanolic extract presented moderate activity against the HepG2 (human hepatocellular carcinoma) and K562 (human chronic myelocytic leukemia) tumor cell lines with IC50 values equal to 46.86 and 35.58 μg/mL, respectively. The alkaloids 7-hydroxynordicentrine, dicentrine, duguetine, and duguetine N-oxide showed promising cytotoxic activity against MCF7 (human breast adenocarcinoma), HCT116 (human colon carcinoma), HepG2, HL-60 (human promyelocytic leukemia) tumor cells with IC50 below 8.0 μg/mL for all cells tested, with except for the duguetine N-oxide compared to the HepG2 line, which had an IC50 of 10.41 μg/mL. 7-hydroxynordicentrine showed potent cytotoxic activity against the MCF7, HCT116 and HL-60 tumor lines with IC50 of 3.41, 1.38 and 0.69 μg/mL, respectively, whereas duguetin showed high cytotoxic activity against the HepG2 lineage (IC50 = 1.78 μg/mL). The results confirm that D. surinamensis is chemically a representative of the Annonaceae family, and a promising source of bioactive substances with potential cytotoxic activity.