Synthesis and potent cytotoxic activity of a novel diosgenin derivative and its phytosomes against lung cancer cells.

Diosgenin (Di), a steroidal sapogenin derived from plants, has been shown to exert anticancer effects in preclinical studies. Using Di as a starting material, various Di derivatives were designed and synthesized, aiming to discover new steroid-based antitumor agents. In this work, we synthesized several Di derivatives and screened FZU-0021-194-P2 (P2), which showed more potent cytotoxic activities against human non-small-cell lung cancer A549 and PC9 cells. Considering that Di has a unique sterol structure similarly to cholesterol, P2 phytosomes (P2Ps) were prepared to further improve the water solubility of P2. The P2Ps exhibited a particle size of 53.6 ± 0.3 nm with oval shape and a zeta potential of -4.0 ± 0.7 mV. P2Ps could inhibit the proliferation of lung cancer cells more efficiently than Di phytosomes after 72 h of incubation time by inducing cell cycle arrest and apoptosis. The results indicated that P2Ps could be a promising anticancer formulation for non-small-cell lung cancer.