Madecassic acid analogues with a five-membered A-ring and their cytotoxic activity

The structural modification of madecassic acid focused on the contraction of the six-membered A-ring to a five-membered ring, combined with the dehydration of 6-OH to form a new double bond and formation of the esterification or amidation at C-28. The synthesised structures were identified based on the analysis of their NMR and EIS-MS data. Eighteen new madecassic acid analogues were tested <i>in vitro</i> for their cytotoxicity against three cancer cell lines, including human mouth carcinoma (KB), human hepatocellular carcinoma (HepG2), and human lung carcinoma (A549) using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Among them, compounds <b>5</b> and <b>12</b> exhibited potent and selective cytotoxic activity in KB and HepG2 cell lines, with IC₅₀ values ranging from 3.57 to 6.32 µM. The results also indicated that analogues with a 5-membered A-ring containing an <i>α</i>,<i>β</i>-unsaturated aldehyde esterified at C-23 showed a decrease in their cytotoxic activity compared to precursors in the tested cancer cells.