Low Catalytic Redox Activity of α-N-Pyridylthiosemicarbazone Iron Complexes Suggests an Indirect ROS Generation Mechanism in Their Biological Activity

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Titel: Low Catalytic Redox Activity of α-N-Pyridylthiosemicarbazone Iron Complexes Suggests an Indirect ROS Generation Mechanism in Their Biological Activity
Autoren: Vinjamuri, Bharath, Kowol, Christian R, Faller, Peter
Quelle: Inorganic Chemistry. 64(40):20340-20347
Verlagsinformationen: AMER CHEMICAL SOC, 2025.
Publikationsjahr: 2025
Schlagwörter: 104004 Chemische Biologie, Molecular Structure, Iron/chemistry, Reactive Oxygen Species/metabolism, Thiosemicarbazones/chemistry, 104004 Chemical biology, Humans, Ascorbic Acid/chemistry, Coordination Complexes/chemistry, 104003 Anorganische Chemie, Oxidation-Reduction, Catalysis, 104003 Inorganic chemistry
Beschreibung: α-N-Pyridylthiosemicarbazones (PTSC) are anticancer agents that can induce oxidative stress in cells, likely through interactions with metal ions. Redox-active Cu and Fe bind strongly to PTSC, forming complexes Cu-PTSC and Fe-PTSC2. These complexes have been proposed to directly catalyze the formation of reactive oxygen species (ROS) and deplete key cellular reductants, thereby exerting oxidative stress. Alternatively, oxidative stress could also arise indirectly through interactions with other cellular targets. Evaluating catalytic rates could help distinguish direct from indirect mechanisms, as ROS production should outpace antioxidant defenses. In this respect, the catalytic activity of the Fe complexes of two PTSCs, Triapine (3AP) and Dp44mT, with the two most abundant reducing agents, ascorbate and glutathione, was evaluated under aerobic conditions. Fe-3AP2 and Fe-Dp44mT2 showed very low catalytic activity in depleting GSH/ascorbate and producing ROS (
Publikationsart: Article
Sprache: English
ISSN: 1520-510X
0020-1669
DOI: 10.1021/acs.inorgchem.5c03520
Zugangs-URL: https://ucrisportal.univie.ac.at/de/publications/5cc12454-44cd-4375-846e-b4476c95e948
Dokumentencode: edsair.dris...00911..67623e416ef95c4c5b99d9f8771cc575
Datenbank: OpenAIRE
Beschreibung
Abstract:α-N-Pyridylthiosemicarbazones (PTSC) are anticancer agents that can induce oxidative stress in cells, likely through interactions with metal ions. Redox-active Cu and Fe bind strongly to PTSC, forming complexes Cu-PTSC and Fe-PTSC2. These complexes have been proposed to directly catalyze the formation of reactive oxygen species (ROS) and deplete key cellular reductants, thereby exerting oxidative stress. Alternatively, oxidative stress could also arise indirectly through interactions with other cellular targets. Evaluating catalytic rates could help distinguish direct from indirect mechanisms, as ROS production should outpace antioxidant defenses. In this respect, the catalytic activity of the Fe complexes of two PTSCs, Triapine (3AP) and Dp44mT, with the two most abundant reducing agents, ascorbate and glutathione, was evaluated under aerobic conditions. Fe-3AP2 and Fe-Dp44mT2 showed very low catalytic activity in depleting GSH/ascorbate and producing ROS (
ISSN:1520510X
00201669
DOI:10.1021/acs.inorgchem.5c03520