The present application provides a derivative with a
repaglinide tetravalent
platinum structure and a preparation method and use thereof, the compound with the
repaglinide tetravalent
platinum structure is shown as general formula (I), wherein, selected from
cisplatin or
oxaliplatin; L is hydroxyl or a series of
repaglinide platinum (IV) compounds targeting p53 pathway described in the present application, which shows good anti-proliferation and anti-
metastasis activity
in vitro and
in vivo. The severe
DNA damage caused by platinum core can up-regulate the expression of p53, and repaglinide (RPG) can also effectively promote the
secretion of p53 through the lumican / p53 / p21 pathway. The present application designs and synthesizes a series of repaglinide tetravalent platinum derivatives, which can start mitochondrial-mediated
apoptosis through the Bcl-2 / Bax /
caspase-3 pathway. Subsequently, with the up-regulation of p53, the compound can effectively activate pro-apoptotic
autophagy, inhibit the epithelial-mesenchymal transition (EMT) process, and then inhibit
tumor angiogenesis by inhibiting COX-2, MMP9 and VEGFA. The compound can also increase the number of CD3 + And CD8 + T cells in tumors by blocking
immune checkpoint PD-L1, and stimulate anti-
tumor immunity. The above multiple anti-tumor mechanisms synergistically inhibit the proliferation and
metastasis of
tumor cells.