# Cytotoxicity of Mimusops caffra-Based Ursolic Acid, Oleanolic Acid and Derivatives Against Human Cancerous and Non-Cancerous Cell Lines

## TL;DR

This study explores the cancer-fighting potential of compounds derived from the Mimusops caffra plant, showing some derivatives are effective against cancer cells with minimal harm to healthy cells.

## Contribution

The study introduces new triterpenoid derivatives of ursolic acid from Mimusops caffra and evaluates their selective cytotoxicity against cancer cells.

## Key findings

- UM (ursolic-28-methylate) showed strong cytotoxicity against cancer cells with minimal impact on non-cancerous cells.
- Methyl addition at C-28 of ursolic acid enhances its anti-cancer activity.
- Ursolic acid derivatives are potential therapeutic agents for breast, liver, and prostate cancers.

## Abstract

According to the World Health Organization, cancer is still the leading cause of death for humans worldwide. Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these drugs. The use of complementary and alternative medicinal products from plants has continued to increase in past decades, due to fewer side effects of bioactive compounds from medicinal plants of which pentacyclic triterpenoids have been identified as one class of secondary metabolites that could play an important role in the treatment and management of a number of non-communicable diseases. The main aim of this study is to extract, isolate, identify, and elucidate pentacyclic triterpenoid (ursolic acid, UA (1), and oleanolic acid, OA (2)) from Mimusops caffra. Semi-synthesis of UA was carried out to obtain some triterpenoid derivatives (3-O-acetyl ursolic acid, AUA (3), ursolic-28-methylate, UM (4), and 3-acetylursolic-methylate, AUM (5)), and we evaluated these compounds as anti-cancer therapeutic agents. Isolation of ursolic acid (UA) (1) from M. caffra is always accompanied by its isomer oleanolic acid (OA) (2) due to their similar retention factors (Rf) values. Acetylation and deacetylation techniques were used to isolate compounds 1 and 2. In vitro cytotoxicity activities of UA, AUA UM, and AUM were evaluated against various cancer cell lines, such as human breast adenocarcinoma cancer cell lines (MDA), human liver cancer cell lines (HepG2), human prostate cancer cell lines (PC3) and non-cancerous human fibroblast cell lines (KMST-6) using MTT assays. The UM exhibited remarkable cytotoxic activities against cancer cells, while little or no activities were observed on non-cancerous cell lines, which indicates that the addition of methyl at C-28 of UA is essential to enhance its activity as a therapeutic agent for cancer. The AUA showed moderate or no cytotoxicity against the different cancer cell lines, which is less than that of the UA parent compound. Moreover, these results suggest that ursolic acid and UA derivatives are potential therapeutic drugs for human breast, liver, and prostate cancers.