Identification of the Marine Alkaloid Lepadin A as Potential Inducer of Immunogenic Cell Death

Abstract

Natural products and their synthetic analogs and derivatives are a traditional source of bioactive molecules with potential development as drug candidates. In this context, Marine Natural Products (MNPs) represent a rich reservoir of diverse molecular skeletons with potential pharmacological activity that, so far, has been mostly explored in cancer and infectious diseases. Starting from the development of a novel bioassay‐guided screening platform for immunomodulatory compounds from an in‐house MNPs library, we report the identification of the alkaloid lepadin A as a new model compound for immune‐based anticancer activity with characteristics that suggest a possible mechanism as Immunogenic Cell Death inducer. The work describes the molecular‐based bioprospecting in the Gulf of Naples together with the bioassay-guided fractionation, the chemical characterization of the alkaloid, and the biological activity in mouse dendritic cells (D1).