# Deciphering Steroidal and Aporphine Alkaloids as Antileukemic Agents by Approaches of Molecular Networking and Metabolomics

## TL;DR

This study identifies steroidal and aporphine alkaloids from plants as potential antileukemic agents using molecular networking and metabolomics.

## Contribution

The novel integration of molecular networking and metabolomics to predict bioactive steroidal and aporphine alkaloids against leukemia.

## Key findings

- Several plant extracts inhibited leukemia cell viability by up to 70% at 100 μg/mL.
- Alkaloid fractions from S. glaucophyllum and O. diospyrifolia showed EC50 values as low as 6.4 μg/mL.
- Boldine demonstrated significant antileukemic activity with EC50 values in the micromolar range.

## Abstract

The chemodiversity of plants is a valuable resource for
drug discovery,
and its combination with modern approaches can reduce the time consumption
for bioactive metabolite discovery. This study aimed to evaluate the
chemical constituents from 18 plant species of different families
against leukemia cancer cells and the application of statistical analysis
from metabolomic data and molecular networking for the prediction
of bioactive metabolites. The samples, extracted by an accelerated
solvent extractor using ethanol and water 7:3 (v/v), were analyzed
by LC-DAD-MS and evaluated against leukemia cancer cells (Kasumi-1,
KG-1, and K-562). Chemical data were aligned, analyzed by statistics,
and applied to create the molecular network. Sesbania
virgata, Aeschynomene denticulata, Erythroxylum angiufugum, Psidium guineense, Astronium fraxinifolium, Coccoloba ochreolata, Solanum glaucophyllum (S. glaucophyllum), and Paullinia pinnata inhibited
K-562 leukemia cancer cell viability by approximately 70% at 100 μg/mL,
while Ocotea diospyrifolia showed 35%
inhibition for the KG-1 lineage. Alkaloid fractions from S. glaucophyllum and O. diospyrifolia revealed EC50 values ranging from 13.9 to 6.4 μg/mL
for K-562 and KG-1 cell lines, effectively inducing cell death with
apoptotic characteristics, membrane integrity loss, and signs of late
apoptosis. The molecular networking was essential and crucial to complement
the statistical analysis, which was performed from 430 features and
targeted steroidal and aporphine alkaloids. Boldine revealed EC50 values of 46, 116, and 145 μM for Kasumi, KG-1, and
K-562 cancer cell lines, respectively. The findings marked the relevance
of a broader chemical data analysis to predict bioactive compounds,
emphasizing potential benefits in the search for metabolites against
leukemia cancer cells, particularly steroidal and aporphine alkaloids.