Design strategy and preliminary antiproliferative investigation of a modified lignan skeleton derived from aryne and statin†

Abstract

The biological activities of natural products (NPs) provided precious resources for the development of new drugs. Numerous studies have shown that statins exhibit cytotoxic potential, which is now an extensive focus of investigation. Herein, a remarkably efficient method for modification of statins using hexadehydro-Diels–Alder (HDDA) arynes has been described. Notably, lactone, as the biologically active group of statins, was removed during the reaction and a novel modified lignan skeleton was generated via the Alder–ene process. Unexpectedly, these statin-derived novel chemical scaffolds exhibited moderate inhibition effects on the proliferation of cancer cells as determined by CCK-8 assays, and the IC₅₀ values were in the micromolar range.