Synthesis, characterization and biological activities of mononuclear Co(III) complexes as potential bioreductively activated prodrugs

Souza, Elizabeth T.; Castro, Lidiane Cavalcante; Castro, Frederico Augusto Vieira de; Visentin, Lorenzo do Canto; Pinheiro, Carlos B.; Pereira, Marcos D.; Machado, Sérgio de Paula; Scarpellini, Marciela

doi:10.1016/j.jinorgbio.2009.07.008

Cited by 26 publications

(13 citation statements)

References 51 publications

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“…Other observed features include the intense π – π* intraligand bands at about 320 nm for all species. These results are in good agreement with the previously published data on cobalt complexes containing [NN′O] donor ligands [10,19]. …”

Section: Resultssupporting

confidence: 93%

“…We also hypothesize that species 1, already containing a labile cobalt(II) species will not remain intact intracellularly in order to reach the targeted proteasome. The possibility of using redox-active metals that can be intracellularly bioreduced opens a stimulating window of opportunity to explore proteasome inhibition, both by metal activation as demonstrated here and as suggested by Scarpellini [10] as well as by using metal ions as carriers for drug delivery [12]. Such studies are currently under investigation in our group.…”

Section: Discussionmentioning

confidence: 85%

“…Similarly we want to compare 1 and 3 to examine the role of the oxidation states and the potential of redox changes in proteasome inhibition. The antitumor activity of cobalt species is fairly understudied, [10] but activity against prostate cancer has been recently demonstrated by McNail et al for bivalent cobalt. [11] On the other hand, Teicher, Ware, Hambley, [12] and more recently Donelly [13] have taken advantage of bioreductive activation of its trivalent counterpart for the treatment of hypoxic tumors.…”

Section: Introductionmentioning

confidence: 99%

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Effects of tethered ligands and of metal oxidation state on the interactions of cobalt complexes with the 26S proteasome

Tomco

Schmitt

Ksebati

et al. 2011

Journal of Inorganic Biochemistry

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In this paper we report on the synthesis and characterization of three cobalt complexes described as [CoII(L1)2] (1), [CoII(L2)] (2), and [CoIII(L1)2]ClO4 (3). These complexes contain the deprotonated forms of the [NN′O] tridentate ligand HL1 and its newly synthesized [N2N′2O2] hexadentate counterpart H2L2, namely, 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol and 6,6′-((ethane-1,2-diylbis((pyridin-2-ylmethyl) azanediyl))bis(methylene))bis(2,4-diiodophenol). Characterizations for 1–3 include electrospray ionization (ESI) spectrometry, infrared, and UV–visible spectroscopies, and elemental analyses. A detailed 1H-NMR study was conducted for 3 and X-ray structural data was obtained for 2. The viability of this series as potential agents for proteasome inhibition and cell apoptotic induction involving PC-3 cancer cells is presented comparing the behavior of the untethered [NN′O]2 six-coordinate 1 and 3 and the tethered counterpart 2 with a 1:1 metal-to-ligand ratio. It is observed that the tethering in 2 decreases inhibition activity. When 1 and 3 are compared, the most inert, but redox-active, cobalt(III) species shows the highest chymotrypsin-like activity inhibition on purified proteasome and PC-3 cancer cells. A hypothesis based on the role of oxidation states for proteasome inhibition is offered.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Effects of tethered ligands and of metal oxidation state on the interactions of cobalt complexes with the 26S proteasome

Tomco

Schmitt

Ksebati

et al. 2011

Journal of Inorganic Biochemistry

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“…The oxidized Co(III) forms were less cytotoxic than the reduced forms, indicating that the Co(III) species serve as prodrugs. A compound analogous to 23 in which the imidazoles were replaced by pyridines behaved similarly [94]. …”

Section: Iron Cobalt Coppermentioning

confidence: 99%

Redox activation of metal-based prodrugs as a strategy for drug delivery

Graf

Lippard

2012

Advanced Drug Delivery Reviews

465

335

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This review provides an overview of metal-based anticancer drugs and drug candidates. In particular, we focus on metal complexes that can be activated in the reducing environment of cancer cells, thus serving as prodrugs. There are many reports of Pt and Ru complexes as redox-activatable drug candidates, but other d-block elements with variable oxidation states have a similar potential to serve as prodrugs in this manner. In this context are compounds based on Fe, Co, or Cu chemistry, which are also covered. A trend in the field of medicinal inorganic chemistry has been toward molecularly targeted, metal-based drugs obtained by functionalizing complexes with biologically active ligands. Another recent activity is the use of nanomaterials for drug delivery, exploiting passive targeting of tumors with nanosized constructs made from Au, Fe, carbon, or organic polymers. Although complexes of all of the above mentioned metals will be described, this review focuses primarily on Pt compounds, including constructs containing nanomaterials.

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“…Além de platina e rutênio, complexos de cobalto também têm sido estudados como PDAHs por possuírem dois estados de oxidação acessíveis, +3 inerte e +2 lábil. 10,13,49,[54][55][56] Os complexos de Co 3+ são inativos e agem como carreadores da droga, desativando-a. No ambiente hipóxico de um tumor, o complexo de Co 3+ é reduzido ao respectivo complexo de Co 2+ , liberando a droga citotóxica coordenada.…”

Section: Figura 12 Complexo De Rutênio Investigado Por Brindell E Counclassified

Redox Activation as Strategy for the Development of New Drugs Applied to the Cancer Treatment

Palmeira-Mello¹,

Lanznaster²

2015

Revista Virtual De Química

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Redox activation has been exploited in the development of drugs for treatment of several diseases, including cancer. Some cancers generate solid tumors that have a poor vascularization, which leads to the generation of hypoxic environments, which in turn, limit the effectiveness of both radio and chemotherapies. These regions have a higher reducing capability when compared to normoxic tissues. Thus, substances capable of circulating intact through the body can be reduced and activated selectively in the hypoxic region of the tumor, becoming cytotoxic. Based on this strategy, five classes of Prodrugs Activated by Hypoxia (PDAHs) are described and include nitro(hetero)cycles (p. eg. nitrogen mustards and nitroimidazoles), aromatic N-oxides, aliphatic Noxides, quinones and transition metal complexes. In this review, some advances in the development of PDAHs are discussed, focusing on the relationship between the redox properties and biological activity.

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Synthesis, characterization and biological activities of mononuclear Co(III) complexes as potential bioreductively activated prodrugs

Cited by 26 publications

References 51 publications

Effects of tethered ligands and of metal oxidation state on the interactions of cobalt complexes with the 26S proteasome

Effects of tethered ligands and of metal oxidation state on the interactions of cobalt complexes with the 26S proteasome

Redox activation of metal-based prodrugs as a strategy for drug delivery

Redox Activation as Strategy for the Development of New Drugs Applied to the Cancer Treatment

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