ArticleJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2013
Metal-drug synergy: new ruthenium(II) complexes of ketoconazole are highly active against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine normal cells.
Article in Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 91 citations in OpenAlex.
- An Experimental and Molecular modelling Study of Ruthenium(II) Polypyridyl Complexes with a Thiazole-Imidazo-Phenanthroline Ligand and their DNA Affinity.Journal of fluorescence · 2026Article
- Ligand-lytic peptides for specific targeting ofFrontiers in cellular and infection microbiology · 2025Article
- The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition.Biomolecules · 2024Review
- Resurgence and Repurposing of Antifungal Azoles by Transition Metal Coordination for Drug Discovery.Pharmaceutics · 2023Review
- Mitochondrial dysfunction on Leishmania (Leishmania) amazonensis induced by ketoconazole: insights into drug mode of action.Memorias do Instituto Oswaldo Cruz · 2022Article
- Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Review
- Ruthenium (II) complex cis-[RuScientific reports · 2020Article
- Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- Ruthenium Complexes as Anticancer Agents: A Brief History and Perspectives.Drug design, development and therapy · 2020Review
- Metal-Ligand Recognition Index Determination by NMR Proton Relaxation Study.Molecules (Basel, Switzerland) · 2019Article
- Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused byMolecules (Basel, Switzerland) · 2018Article
- Ruthenium-Clotrimazole complex has significant efficacy in the murine model of cutaneous leishmaniasis.Acta tropica · 2016Article
- Novel arylalkylamine compounds exhibits potent selective antiparasitic activity against Leishmania major.Bioorganic & medicinal chemistry letters · 2015Article
- In vitro effects of binuclear (η (6)-p-cymene)ruthenium(II) complex containing bridging bis(nicotinate)-polyethylene glycol ester ligand on differentiation pathways of murine Th lymphocytes activated by T cell mitogen.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Ruthenium complex with benznidazole and nitric oxide as a new candidate for the treatment of chagas disease.PLoS neglected tropical diseases · 2014Article
- Nitro/nitrosyl-ruthenium complexes are potent and selective anti-Trypanosoma cruzi agents causing autophagy and necrotic parasite death.Antimicrobial agents and chemotherapy · 2014Article
- Analysis of the cytotoxic effects of ruthenium-ketoconazole and ruthenium-clotrimazole complexes on cancer cells.Cell biology and toxicology · 2013Article
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8 authors at 5 institutions in 1 country.
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Abstract
In our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and Chagas disease, six new ruthenium-ketoconazole (KTZ) complexes have been synthesized and characterized, including two octahedral coordination complexes-cis,fac-[Ru(II)Cl2(DMSO)3(KTZ)] (1) and cis-[Ru(II)Cl2(bipy)(DMSO)(KTZ)] (2) (where DMSO is dimethyl sulfoxide and bipy is 2,2'-bipyridine)-and four organometallic compounds-[Ru(II)(η(6)-p-cymene)Cl2(KTZ)] (3), [Ru(II)(η(6)-p-cymene)(en)(KTZ)][BF4]2 (4), [Ru(II)(η(6)-p-cymene)(bipy)(KTZ)][BF4]2 (5), and [Ru(II)(η(6)-p-cymene)(acac)(KTZ)][BF4] (6) (where en is ethylenediamine and acac is acetylacetonate); the crystal structure of 3 is described. The central hypothesis of our work is that combining a bioactive compound such as KTZ and a metal in a single molecule results in a synergy that can translate into improved activity and/or selectivity against parasites. In agreement with this hypothesis, complexation of KTZ with Ru(II) in compounds 3-5 produces a marked enhancement of the activity toward promastigotes and intracellular amastigotes of Leishmania major, when compared with uncomplexed KTZ, or with similar ruthenium compounds not containing KTZ. Importantly, the selective toxicity of compounds 3-5 toward the leishmania parasites, in relation to human fibroblasts and osteoblasts or murine macrophages, is also superior to the selective toxicities of the individual constituents of the drug. When tested against Trypanosoma cruzi epimastigotes, some of the organometallic complexes displayed activity and selectivity comparable to those of free KTZ. A dual-target mechanism is suggested to account for the antiparasitic properties of these complexes.
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