Novel platinum(iv) complexes were synthesised to examine the facile modulation of the lipophilicity of the complex by incorporating axial ligands of increasing length, ranging from 2-6 carbons. RP-HPLC was used to establish the lipophilicity of each complex. The in vitro cytotoxicities of all complexes were determined against a panel of malignant cell lines and a non-cancerous cell line. While there was no clear correlation between lipophilicity and cytotoxicity, all complexes demonstrated nanomolar activity against all cell lines. The most potent complexes exhibited 850-fold greater activity than cisplatin against HT29 colon carcinoma with GI50 values of 13 nM.
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J Control Release
January 2025
Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin 300070, China. Electronic address:
Platinum(II)-based antitumor drugs are widely used in clinics but limited by severe side effects and resistance. Multi-target Platinum(IV) complexes are emerging as ideal alternatives. Heme oxygenase-1 (HO-1) works as a rate-limiting step in heme degradation and is overexpressed in malignant tumors.
View Article and Find Full Text PDFDalton Trans
January 2025
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119334, Vavilova Str., 28, bld. 1, Moscow, Russia.
A low oxygen level in solid tumors is behind the modern concept of selective chemotherapy by hypoxia-activated prodrugs, such as heteroleptic complexes of transition metals (cobalt(III), iron(III) or platinum(IV)) with bi- or tetradentate ligands and an anticancer drug molecule as a co-ligand. A series of new cobalt(III) complexes [Co(LR)(esc)]ClO with esculetin (6,7-dihydroxycoumarin) and 2,2'-bipyridines (2,2'-bipy) functionalized by different substituents R were probed in the hypoxia-activated delivery of this model anticancer drug. Their combined study by cyclic voltammetry and NMR spectroscopy allowed identifying linear correlations of the electrochemical reduction potentials and the rate of the hypoxia-activated dissociation of [Co(LR)(esc)]ClO with the Hammett constants of the substituents in 2,2'-bipy ligands.
View Article and Find Full Text PDFInorg Chem Front
January 2025
Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria +43 (0)1 40160-57557.
Platinum chemotherapy is part of every second anticancer treatment regimen. However, its application is limited by severe side effects and drug resistance. The combination of platinum-based chemotherapeutics with EGFR inhibitors has shown remarkable synergism in clinical treatment.
View Article and Find Full Text PDFDalton Trans
January 2025
Department of Chemistry, Babeş-Bolyai University, Str. Arany Janos Nr. 11, RO-400028 Cluj-Napoca, Romania.
The synthesis and characterization of novel platinum(II) and platinum(IV) complexes derived from unsymmetrical ethylene or propylenediamine derivatives are presented. IR spectroscopy and ESI mass spectrometry techniques were employed to characterize the complexes, revealing distinctive absorption bands and isotope patterns. Furthermore, the complexes were characterized by H and C NMR spectroscopy.
View Article and Find Full Text PDFACS Cent Sci
December 2024
Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Over 90% of cancer patients succumb to metastasis, yet conventional frontline therapy struggles to halt the progression of metastatic tumors. Targeted radionuclide therapy, which delivers radiation precisely to tumor sites, shows promise for treating metastasis. The rational design of a prodrug activation platform using radionuclides would be an ideal approach to synergize chemotherapy with targeted radionuclide therapy, yet it has not been established.
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