A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL-2.

Autor: Bannwart F; Department of Human Medicine, MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany.; Department of Pediatric Hematology/Oncology, Helios Kliniken Schwerin, Wismarsche Str. 393-397, 19055 Schwerin, Germany., Richter LF; Department of Chemistry and Catalysis Research Center, Molecular Catalysis, Technical University of Munich, TUM School of Natural Sciences, Lichtenbergstr. 4, 85748 Garching bei München, Germany., Stifel S; Department of Chemistry and Catalysis Research Center, Molecular Catalysis, Technical University of Munich, TUM School of Natural Sciences, Lichtenbergstr. 4, 85748 Garching bei München, Germany., Rueter J; Department of Human Medicine, MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany.; Department of Pediatric Hematology/Oncology, Helios Kliniken Schwerin, Wismarsche Str. 393-397, 19055 Schwerin, Germany., Lode HN; Department of Pediatric Hematology/Oncology, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. 1, 17475 Greifswald, Germany., Correia JDG; Centro de Ciências e Tecnologias Nucleares and Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Bobadela, Lisbon, LRS 2695-066, Portugal., Kühn FE; Department of Chemistry and Catalysis Research Center, Molecular Catalysis, Technical University of Munich, TUM School of Natural Sciences, Lichtenbergstr. 4, 85748 Garching bei München, Germany., Prokop A; Department of Human Medicine, MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany.; Department of Pediatric Hematology/Oncology, Helios Kliniken Schwerin, Wismarsche Str. 393-397, 19055 Schwerin, Germany.; Experimental Oncology, Municipal Hospitals of Cologne, Ostmerheimer Str. 200, 51109 Cologne, Germany.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2024 Sep 12; Vol. 67 (17), pp. 15494-15508. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1021/acs.jmedchem.4c01117
Abstrakt: From previous studies, it is evident that metal-organic gold(I) complexes have antiproliferative activities. The aim of this study is not only to find new anticancer agents but also to overcome existing cytostatic resistance in cancer cells. The synthesis and medicinal evaluation of two cationic 1,3-disubstituted gold(I) bis-tetrazolylidene complexes 1 and 2 are reported. To determine apoptosis-inducing properties of the complexes, DNA fragmentation was measured using propidium iodide staining followed by flow cytometry. Gold(I) complex 1 targets explicitly malignant cells, effectively inhibiting their growth and selectively inducing apoptosis without signs of necrosis. Even in cells resistant to common treatments such as doxorubicin, it overcomes multidrug resistance and sensitizes existing drug-resistant cells to common cytostatic drugs. It is assumed that gold(I) complex 1 involves the mitochondrial pathway in apoptosis and targets members of the BCL-2 family, enhancing its potential as a therapeutic agent in cancer treatment.
Databáze: MEDLINE