Synthesis and cytotoxic activity of triphenylphosphonium salts of ecdysteroids, lithocholic acid and cholesterol

Phytoecdysteroid 20-hydroxyecdysone (20E, <b>1</b>) has been isolated from the plant <i>Serratula coronata</i> L. (Asteraceae). Acetonide (<b>2</b>) and short-chain (<b>3</b>) derivatives of 20E, along with lithocholic acid and cholesterol, were used as starting materials for the synthesis of their triphenylphosphonium salts (TPP⁺). These compounds were screened for cytotoxicity and selectivity against several human non-small cell lung (NSCLC) cancer cell lines and non-cancerous (mesenchymal stem cell (MSCs)) lines using the MTT assay. The results demonstrated that the parent compounds - (ecdysteroids (<b>1-3</b>), lithocholic acid (<b>8</b>), and cholesterol (<b>9</b>) - were non-toxic to all tested cell lines. In contrast, all synthesised derivatives, particularly TPP⁺ salt of lithocholic acid (<b>12</b>), exhibited preferential cytotoxicity against NSCLC cell lines at micromolar concentrations (IC₅₀ 1-1.7 µM). The AnnexinV/7-AAD flow cytometry assay confirmed the selective cytotoxicity of all TPP⁺ derivatives towards NSCLC cells, with minimal effects on non-cancerous MSCs.