Calquiquelignan D from Attalea butyracea Exhibits Selective Cytotoxicity Against Prostate and Skin Cancer Cells with...

Skin and prostate cancers pose therapeutic challenges due to drug resistance. Attalea butyracea, a Neotropical palm with profound ethnobotanical significance, remains largely unexplored for anticancer constituents. This study aimed to isolate bioactive metabolites from A. butyracea, assess their selective cytotoxicity against A-431 and PC-3 cancer cells relative to normal cells, and explore their potential molecular targets. High-Resolution Electrospray Ionization Mass Spectrometry (HR-ESI/MS) and one- and two-dimensional nuclear magnetic resonance (1D/2D NMR) spectroscopy provided structural confirmation. Cytotoxic activity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Computational inverse docking and molecular dynamics simulations identified probable kinase targets, which were subsequently confirmed through enzyme inhibition assays. Phytochemical investigation yielded 17 compounds, including two previously undescribed glycosides, one megastigmane, and one flavonolignan. This marks the first report of flavonolignans within Attalea. Among isolated metabolites, calquiquelignan D showed notable activity, with CC₅₀ values of 14.9 μM (A431) and 22.5 μM (PC3), comparable to those of cisplatin. Within the ATP pockets of oncogenic kinases, this compound demonstrated stable binding patterns as determined by computational analysis. Enzyme inhibition assays confirmed dual inhibition of ERK2 and PI3Kα at nanomolar concentrations. These findings suggest potential dual-pathway modulation of survival signaling. As chemotaxonomic markers with structurally distinct scaffolds, these metabolites merit further kinase-targeted drug development.