New modified silybin derivatives: design, synthesis, and preliminary evaluation of antitumor activity

Based on the molecular docking of Epidermal Growth Factor Receptor inhibitors and known small molecules, key amino acid fragments and active groups were analyzed through computer-aided drug design techniques. Subsequently, these active functional groups were introduced at positions C-23 and C-7 of silybin to design and synthesize 12 novel silybin derivatives. The structures of these innovative silybin analogues were confirmed by nuclear magnetic resonance and mass spectrometry. Moreover, the antitumor activities of these novel analogues were evaluated by MTT assay. As a result, compounds <b>I₂</b> and <b>I₈</b> exhibited greater cytotoxicity against tumor cells compared to silybin and positive control drugs such as gefitinib. In conclusion, our study synthesized 12 novel silybin derivatives and identified compounds <b>I₂</b> and <b>I₈</b> as potential candidates or cancer therapy.