title: Increasing the activity of copper(II) complexes against Leishmania through lipophilicity and pro-oxidant ability.
abstract: Copper complexes with fluorinated β-diketones were synthesized and characterized in terms of lipophilicity and peroxide-assisted oxidation of dihydrorhodamine as an indicator of redox activity. The biological activity of the complexes was tested against promastigotes of Leishmania amazonensis. Inhibition of trypanosomatid-specific trypanothione reductase was also tested. It was found that the highly lipophilic and redox-active bis(trifluoroacetylacetonate) derivative had increased toxicity towards promastigotes. These results indicate that it is possible to modulate the activity of metallodrugs based on redox-active metals through the appropriate choice of lipophilic chelators in order to design new antileishmanials. Further work will be necessary to improve selectivity of these compounds against the parasite.
authors.affiliation: Instituto de Química, Universidade de São Paulo, Av Lineu Prestes 748, 05508-000 São Paulo, SP, Brazil.
authors.forename: Andressa dos Santos
authors.initials: Ados S
authors.lastname: Portas
authors.forename: Danilo Ciccone
authors.initials: DC
authors.lastname: Miguel
authors.forename: Jenicer K U
authors.initials: JK
authors.lastname: Yokoyama-Yasunaka
authors.forename: Silvia Reni Bortolin
authors.initials: SR
authors.lastname: Uliana
authors.forename: Breno Pannia
authors.initials: BP
authors.lastname: Espósito
mesh_terms: D003300:Copper / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry; D007894:Leishmania mexicana / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007659:Ketones; D008055:Lipids; D009942:Organometallic Compounds; D016877:Oxidants; D003300:Copper; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase