Targeted Isolation of Cytotoxic Sesquiterpene Lactones from Eupatorium fortunei 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 Eupatorium fortunei with the aid of structural annotation by SMART 2.0 and chemical profiling. Eight germacrene-type ( 1–7 and 10 ) and two eudesmane-type sesquiterpene lactones ( 8 and 9 ) were isolated from the whole plant of Eupatorium fortunei . With the guidance of the results of the subfractions from E. fortunei obtained by SMART 2.0, their cytotoxic activities were evaluated against five cancer cells (SKOV3, A549, PC3, HEp-2, and MCF-7). Compounds 4 and 8 exhibited IC 50 values of 3.9 ± 1.2 and 3.9 ± 0.6 μM against prostate cancer cells, PC3, respectively. Compound 7 showed good cytotoxicity with IC 50 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.

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

“…Despite the majority of the computational screening approaches using ML algorithms lacking experimental validations, we have some interesting successful studies that aimed to find and characterize novel natural products with experimentally validated biological activity (Rupp et al, 2010 ; Zhang et al, 2017 ; Nocedo-Mena et al, 2019 ; Patsilinakos et al, 2019 ; Lee et al, 2020 ; Liu et al, 2020 ). Recently, Reher et al reported on the SMART 2.0, an NMR-based machine learning tool designed for the discovery and characterization of natural products.…”

“…Similarly, Lee et al applied SMART 2.0 to prioritize the isolation and characterization of sesquiterpene lactones from the Eupatorium fortune plant. The isolated natural compounds were experimentally tested against five cancer cell lines and exhibited cytotoxic activities (Lee et al, 2020 ).…”

An insight into cytotoxic activity of flavonoids and sesquiterpenoids from selected plants of Asteraceae species

“…Three germacranolide sesquiterpene lactones, (macrocephalides A-C) 74-76(Figure 5) were isolated from Eupatorium macrocephalum. 74 and 75 showed potent cytotoxicity (Lee et al, 2020). However, 76 showed moderate cytotoxicity in various tumour cell lines (Yang et al, 2019).…”

Anti-inflammatory Eudesmane Sesquiterpenoids from Artemisia hedinii

“…The final R 1 was 0.0358 (I > 2σ(I)) and wR 2 was 0.0936. Flack parameter: −0.01 (10). Crystallographic data for 1 have been deposited at the Cambridge Crystallographic Data Centre as deposit no.…”

“…C 17 H 24 O 6 : M = 324.36 g/mol, orthorhombic, space group P2 1 2 1 2 1 (no. 19), a = 6.64130 (10) Å, b = 14.8419(3) Å, c = 16.7613(3) Å, α = 90°, β = 90°, γ = 90°, V = 1652.15(5) Å 3 , Z = 4, T = 140 K, μ(Cu Kα) = 0.815 mm −1 , D calc = 1.304 g/cm 3 , 23 113 reflections measured (7.956°≤ 2σ ≤ 149.016°), 3375 unique (R int = 0.0380, R sigma = 0.0212), which were used in all calculations. The final R 1 was 0.0282 (I > 2σ(I)) and wR 2 was 0.0722.…”