Targeted Isolation of Cytotoxic Sesquiterpene Lactones from <i>Eupatorium fortunei</i> by the NMR Annotation Tool, SMART 2.0

Abstract

Small Molecular Accurate Recognition Technology (SMART 2.0) has recently been introduced as a NMR-based machine learning tool for the discovery and characterization of natural products. We attempted targeted isolation of sesquiterpene lactones from <i>Eupatorium fortunei</i> with the aid of structural annotation by SMART 2.0 and chemical profiling. Eight germacrene-type (<b>1-7</b> and <b>10</b>) and two eudesmane-type sesquiterpene lactones (<b>8</b> and <b>9</b>) were isolated from the whole plant of <i>Eupatorium fortunei</i>. With the guidance of the results of the subfractions from <i>E. fortunei</i> obtained by SMART 2.0, their cytotoxic activities were evaluated against five cancer cells (SKOV3, A549, PC3, HEp-2, and MCF-7). Compounds <b>4</b> and <b>8</b> exhibited IC₅₀ values of 3.9 ± 1.2 and 3.9 ± 0.6 μM against prostate cancer cells, PC3, respectively. Compound <b>7</b> showed good cytotoxicity with IC₅₀ values of 5.8 ± 0.1 μM against breast cancer cells, MCF-7. In the present study, the rapid annotation of the mixture of compounds in a fraction by the NMR-based machine learning tool helped the targeted isolation of bioactive compounds from natural products.