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

鉴定海洋生物碱 Lepadin A 为免疫原性细胞死亡的潜在诱导剂

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作者:Genoveffa Nuzzo, Carmela Gallo, Fabio Crocetta, Lucia Romano, Giusi Barra, Giuseppina Senese, Mario dell'Isola, Dalila Carbone, Valentina Tanduo, Federica Albiani, Guido Villani, Giuliana d'Ippolito, Emiliano Manzo, Angelo Fontana

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).

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