Synthesis and Biological Evaluation of Novel Meroterpenoid Derivatives against Cisplatin-Induced Acute Kidney Injury.

Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs () and 40 simplifiers () were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of . Among these compounds, showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) and , and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that promoted the efflux of cisplatin upregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.