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Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2024 Jul 11; Vol. 67 (13), pp. 11086-11102. Date of Electronic Publication: 2024 Jun 26. - Publication Year :
- 2024
-
Abstract
- Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31 . This study shows that Ru-STF31 can significantly decrease intracellular NAD <superscript>+</superscript> levels in both normoxic (21% O <subscript>2</subscript> ) and hypoxic (1% O <subscript>2</subscript> ) U87MG cells. Strikingly, NAD <superscript>+</superscript> depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD <superscript>+</superscript> . Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.
- Subjects :
- Humans
Cell Line, Tumor
Cytokines metabolism
Light
Enzyme Inhibitors pharmacology
Enzyme Inhibitors chemistry
Enzyme Inhibitors chemical synthesis
Nicotinamide Phosphoribosyltransferase antagonists & inhibitors
Nicotinamide Phosphoribosyltransferase metabolism
Ruthenium chemistry
Ruthenium pharmacology
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents chemical synthesis
Oxygen metabolism
NAD metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 67
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38924492
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.4c00589