A Cytotoxic Porphyrin from North Pacific Brittle Star <i>Ophiura sarsii</i>
Antonina Klimenko,
Robin Huber,
Laurence Marcourt,
Estelle Chardonnens,
Alexey Koval,
Yuri S. Khotimchenko,
Emerson Ferreira Queiroz,
Jean-Luc Wolfender,
Vladimir L. Katanaev
Affiliations
Antonina Klimenko
Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
Robin Huber
School of Pharmaceutical Sciences, University of Geneva, CMU—Rue Michel-Servet 1, CH-1211 Geneva, Switzerland
Laurence Marcourt
School of Pharmaceutical Sciences, University of Geneva, CMU—Rue Michel-Servet 1, CH-1211 Geneva, Switzerland
Estelle Chardonnens
Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
Alexey Koval
Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
Yuri S. Khotimchenko
School of Biomedicine, Far Eastern Federal University, 690090 Vladivostok, Russia
Emerson Ferreira Queiroz
School of Pharmaceutical Sciences, University of Geneva, CMU—Rue Michel-Servet 1, CH-1211 Geneva, Switzerland
Jean-Luc Wolfender
School of Pharmaceutical Sciences, University of Geneva, CMU—Rue Michel-Servet 1, CH-1211 Geneva, Switzerland
Vladimir L. Katanaev
Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland
Triple-negative breast cancer (TNBC) represents the deadliest form of gynecological tumors currently lacking targeted therapies. The ethanol extract of the North Pacific brittle star Ophiura sarsii presented promising anti-TNBC activities. After elimination of the inert material, the active extract was submitted to a bioguided isolation approach using high-resolution semipreparative HPLC-UV, resulting in one-step isolation of an unusual porphyrin derivative possessing strong cytotoxic activity. HRMS and 2D NMR resulted in the structure elucidation of the compound as (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid. Never identified before in Ophiuroidea, porphyrins have found broad applications as photosensitizers in the anticancer photodynamic therapy. The simple isolation of a cytotoxic porphyrin from an abundant brittle star species we describe here may pave the way for novel natural-based developments of targeted anti-cancer therapies.
