A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells. (9th August 2017)

• Record Type: Journal Article
• Authors: Lameijer, Lucien N.; Ernst, Daniël; Hopkins, Samantha L.; Meijer, Michael S.; Askes, Sven H. C.; Le Dévédec, Sylvia E.; Bonnet, Sylvestre
• Is Part Of: Angewandte Chemie. Volume 129:Number 38(2017)
• Page Start: 11707
• Page End: 11711
• Publication Date: 2017-08-09
• Subjects: Hypoxie -- Photopharmakologie -- Rotlichtaktivierung -- Ruthenium -- Tumortherapeutika; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201703890
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: We describe two water‐soluble ruthenium complexes, [1 ]Cl2 and [2 ]Cl2, that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm −2 ) of red light in an oxygen‐independent manner. Using a specific NAMPT activity assay, up to an 18‐fold increase in inhibition potency was measured upon red‐light activation of [2 ]Cl2, while [1 ]Cl2 was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O2 ). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [2 ]Cl2, whether the cells were cultured and irradiated with 1 % or 21 % O2 . These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.