Estudo químico e avaliação da citotoxicidade do extrato etanólico e frações de Cereus jamacaru DC. (Cactaceae)

Abstract

This study evaluated the cytotoxic potential of the ethanolic extract from Cereus jamacaru cladodes and its fractions against the HCT-116 (colorectal carcinoma) cell line, correlating bioactivity with the chemical profile obtained by chromatography and mass spectrometry. The extract was partitioned into hexane, dichloromethane, ethyl acetate, and hydromethanolic phase, with similar yields among the organic fractions and predominance of the polar phase. Cytotoxicity was determined using the MTT assay, with an initial screening at 50 and 5 µg/mL and IC50 determination for the active samples. Chemical characterization employed UHPLC–ESI–MS/MS for low-volatility/thermolabile compounds and GC–EI–MS (70 eV) for volatile and semi-volatile ones. Molecular networks (GNPS) were generated with cosine ≥ 0.7 and ≥ 6 matched peaks and visualized in Cytoscape. In screening at 50 µg/mL, FHC showed the highest inhibition (88.59 ± 10.88%), followed by the ethanolic extract (59.17 ± 4.17%) and FDC (65.91 ± 14.03%), while FAC was less active (38.29 ± 7.41%). As a positive control, doxorubicin (DOX) showed inhibition of 88.95 ± 0.76%. Subfractionation maintained high performance (≥ 75% inhibition in 16 FHC subfractions and 10 FDC subfractions). The IC50 values confirmed the greater potency for FHC (41.30 µg/mL) and FDC (46.61 µg/mL), with emphasis on the subfractions of FHC (≈43–58 µg/mL) and FD-3 (39.02 µg/mL). Fatty acids and their derivatives were mostly annotated, such as lauric acid, palmitic acid, ethyl palmitate, methyl linoleate, and phytol, which is consistent with the greater effect of the less polar fractions. Analyses in ESI+ and ESI– showed preferential detection of neutral lipids and terpenoids in the positive mode, and of more polar and acidic compounds in the negative mode. The results indicate that Cereus jamacaru is a promising source of cytotoxic metabolites against HCT-116, with emphasis on apolar fractions, and that the integration between UHPLC–ESI–MS/MS and GC–EI–MS, associated with GNPS networks, allowed linking chemical class (fatty acid derivatives, esters, and terpenoids) to bioactivity, providing a robust framework for future studies of isolation, structural elucidation, and investigation of mechanisms of action.