# Exploring the Anticancer Potential of Phenolic nor-Triterpenes from Celastraceae Species

## TL;DR

This study identifies new anticancer compounds from Celastraceae plants that show promise against various human tumor cell lines.

## Contribution

The discovery of three novel phenolic nor-triterpenes with significant antitumor activity and insights into their structure-activity relationships.

## Key findings

- Three compounds (6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral) showed significant antitumor activity against multiple human cancer cell lines.
- Apoptosis was identified as the mode of action in HeLa cells for these compounds.
- Oxidative stress and mitochondrial dysfunction were ruled out as mechanisms of action for the active compounds.

## Abstract

To explore new compounds with antitumour activity, fifteen phenolic nor-tripterpenes isolated from Celastraceae species, Maytenus jelskii, Maytenus cuzcoina, and Celastrus vulcanicola, have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI50 ranging from 0.45 to 8.6 µM) on at least five of the cell lines tested. Continuous live cell imaging identified apoptosis as the mode of action of selective cell killing in HeLa cells. Furthermore, their effect on a drug-sensitive Saccharomyces cerevisiae strain has been investigated to deepen on their mechanism of action. In dose-response growth curves, zeylasteral and 7α-hydroxy-blepharodol were markedly active. Additionally, halo assays were conducted to assess the involvement of oxidative stress and/or mitochondrial function in the anticancer profile, ruling out these modes of action for the active compounds. Finally, we also delve into the structure-activity relationship, providing insights into how the molecular structure of these compounds influences their biological activity. This comprehensive analysis enhances our understanding of the therapeutic potential of this triterpene type and underscores its relevance for further research in this field.