Gold(I) Bis(1,2,3-triazol-5-ylidene) Complexes as Promising Selective Anticancer Compounds.

Autor:	Schlagintweit JF; Molecular Catalysis, Catalysis Research Center and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, Garching bei München D-85748, Germany., Jakob CHG; Molecular Catalysis, Catalysis Research Center and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, Garching bei München D-85748, Germany., Wilke NL; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany.; Department of Pediatric Oncology/Hematology, Helios Clinics Schwerin, Wismarsche Straße 393-397, 19049 Schwerin, Germany.; MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany., Ahrweiler M; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany.; Department of Pediatric Oncology/Hematology, Helios Clinics Schwerin, Wismarsche Straße 393-397, 19049 Schwerin, Germany., Frias C; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany.; Department of Pediatric Oncology/Hematology, Helios Clinics Schwerin, Wismarsche Straße 393-397, 19049 Schwerin, Germany.; MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany., Frias J; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany.; Department of Pediatric Oncology/Hematology, Helios Clinics Schwerin, Wismarsche Straße 393-397, 19049 Schwerin, Germany.; MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany., König M; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany., Esslinger EHJ; Molecular Catalysis, Catalysis Research Center and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, Garching bei München D-85748, Germany., Marques F; Centro de Ciências e Tecnologias Nucleares and Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), Bobadela LRS 2695-066, Portugal., Machado JF; Centro de Ciências e Tecnologias Nucleares and Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), Bobadela LRS 2695-066, Portugal.; Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisboa 1749-016, Portugal., Reich RM; Molecular Catalysis, Catalysis Research Center and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, Garching bei München D-85748, Germany., Morais TS; Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisboa 1749-016, Portugal., Correia JDG; Centro de Ciências e Tecnologias Nucleares and Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), Bobadela LRS 2695-066, Portugal., Prokop A; Department of Pediatric Hematology/Oncology, Children's Hospital Cologne, Amsterdamer Straße 59, Cologne 50735, Germany.; Department of Pediatric Oncology/Hematology, Helios Clinics Schwerin, Wismarsche Straße 393-397, 19049 Schwerin, Germany.; MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany., Kühn FE; Molecular Catalysis, Catalysis Research Center and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, Garching bei München D-85748, Germany.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2021 Nov 11; Vol. 64 (21), pp. 15747-15757. Date of Electronic Publication: 2021 Oct 20.
DOI:	10.1021/acs.jmedchem.1c01021
Abstrakt:	The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC 50 values of 50 nM (lymphoma cells) and 500 nM (leukemia cells), respectively (Mes < iPr). The compounds exclusively induce apoptosis (50 nM to 5 μM) instead of necrosis in common malignant blood cells (leukemia cells) and do not affect non-malignant leucocytes. Remarkably, the complexes not only overcome resistances against the well-established cytostatic etoposide, cytarabine, daunorubicin, and cisplatin but also promote a synergistic effect of up to 182% when used with daunorubicin. The present results demonstrate that gold(I) bis(1,2,3-triazol-5-ylidene) complexes are highly promising and easily modifiable anticancer metallodrugs.
Databáze:	MEDLINE
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