Design, synthesis, and activity evaluation of alpinetin derivatives as potential anti-liver cancer drugs.

Liver cancer represents a major global health challenge, significantly impacting populations both in China and worldwide. Alpinetin (ALP), extracted from the ginger plant cardamom, has been shown to possess significant anti-liver cancer activity. However, its solubility and mechanism of action remain unclear, hindering its further development and application. Heat shock protein 70 (HSP70) has been proven to be a potential target for the treatment of liver cancer. Based on rational drug design principles, ALP was conjugated with specific pharmacophores through oxime linkages to yield novel compounds, aiming to reduce toxicity and enhanced activity. Thus, representative compounds 1a and 1b were obtained. Then, the preliminary mechanism of action was further investigated. Western blot analysis results indicate that compounds 1a and 1b could inhibit the expression of HSP70 protein in HepG2 liver cancer cells. Cell apoptosis data indicate that the synthesized compounds exert anticancer activity by inducing apoptosis. Therefore, this study suggests that ALP and its derivatives may become promising drugs for exerting anti liver cancer effects by regulating the expression of HSP70 protein.