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A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells

Title	A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells
Authors	Lucien N. Lameijer, Daniël Ernst, Dr. Samantha L. Hopkins, Michael S. Meijer, Dr. Sven H. C. Askes, Dr. Sylvia E. Le Dévédec, Dr. Sylvestre Bonnet
Magazine	Angewandte Chemie (International Ed. in English)
Date	08/09/2017
DOI	10.1002/anie.201703890
Introduction	In this study, we present two water-soluble ruthenium complexes, [1]Cl2 and [2]Cl2, which release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor under low-dose red light, independent of oxygen. Upon red-light activation, the inhibition potency of [2]Cl2 significantly increased by up to 18-fold, while [1]Cl2 was found to be thermally unstable. The cytotoxicity of these photocaged compounds was evaluated under hypoxia (1% O2), revealing a 3- to 4-fold increase in cytotoxicity in skin (A431) and lung (A549) cancer cells upon red-light irradiation, regardless of oxygen levels (1% or 21% O2). These findings highlight the potential for photoactivated chemotherapy in treating hypoxic cancer cells, where traditional photodynamic therapy is less effective due to its reliance on oxygen activation.
Quote	Lucien N. Lameijer, Daniël Ernst and Samantha L. Hopkins et al. A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells. Angew. Chem. Int. Ed. Engl. 2017. Vol. 56(38):11549-11553. DOI: 10.1002/anie.201703890
Element	Ruthenium (Ru) , Oxygen (O)
Materials	Chemical Compounds
Industry	Pharmaceutical Industry

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