Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone-Receptor Affinity of Several Organometallic Groups at the 17 Position

Top, Siden; Hafa, Hassane El; Vessières, Anne; Huché, Michel; Vaissermann, Jacqueline; Jaouen, Gérard

doi:10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m

Cited by 41 publications

(30 citation statements)

References 23 publications

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“…Their application in cancer therapy, drug-receptor interaction, and malaria is so promising to the extent that "bio-organometallic chemistry" has now become an emerging discipline that may offer innovative solutions to biological problems. [27][28][29][30] Our group recently corroborated this view in finding that two metal carbonyls, dimanganese decacarbonyl and tricarbonyldichlororuthenium (II) dimer, modulate vessel relaxation and acute hypertension by liberating CO in vitro and in vivo. 23 These data not only provided the first direct evidence that transition metal carbonyls have the ability to function as CO-releasing molecules (CO-RMs) in biological systems, but also emphasized their use as important tools to better identify intracellular targets of CO and elucidate its mechanism(s) of action.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Actions by a Water-Soluble Carbon Monoxide–Releasing Molecule

Clark

Naughton

Shurey

et al. 2003

Circulation Research

623

640

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Abstract-Carbon monoxide, which is generated in mammals during the degradation of heme by the enzyme heme oxygenase, is an important signaling mediator. Transition metal carbonyls have been recently shown to function as carbon monoxide-releasing molecules (CO-RMs) and to elicit distinct pharmacological activities in biological systems.In the present study, we report that a water-soluble form of CO-RM promotes cardioprotection in vitro and in vivo. Specifically, we found that tricarbonylchloro(glycinato)ruthenium(II) (CORM-3) is stable in water at acidic pH but in physiological buffers rapidly liberates CO in solution. Cardiac cells pretreated with CORM-3 (10 to 50 mol/L) become more resistant to the damage caused by hypoxia-reoxygenation and oxidative stress. In addition, isolated hearts reperfused in the presence of CORM-3 (10 mol/L) after an ischemic event displayed a significant recovery in myocardial performance and a marked and significant reduction in cardiac muscle damage and infarct size. The cardioprotective effects mediated by CORM-3 in cardiac cells and isolated hearts were totally abolished by 5-hydroxydecanoic acid, an inhibitor of mitochondrial ATP-dependent potassium channels. Predictably, cardioprotection is lost when CORM-3 is replaced by an inactive form (iCORM-3) that is incapable of liberating CO. Using a model of cardiac allograft rejection in mice, we also found that treatment of recipients with CORM-3 but not iCORM-3 considerably prolonged the survival rate of transplanted hearts. These data corroborate the notion that transition metal carbonyls could be used as carriers to deliver CO and highlight the bioactivity and potential therapeutic features of CO-RMs in the mitigation of cardiac dysfunction. Key Words: transition metal carbonyls Ⅲ carbon monoxide-releasing molecules Ⅲ myocardial ischemia Ⅲ heart transplantation Ⅲ reperfusion injury M ammalian cells constantly generate carbon monoxide (CO) gas via the endogenous degradation of heme by a family of constitutive (HO-2) and inducible (HO-1) heme oxygenase enzymes. 1,2 Firstly described as a putative neural messenger, 3 CO is now regarded as a versatile signaling molecule having essential regulatory roles in a variety of physiological and pathophysiological processes that take place within the cardiovascular, nervous, and immune systems. Indeed, CO produced in the vessel wall by heme oxygenase enzymes possesses vasorelaxing properties and has been shown to prevent vasoconstriction and both acute and chronic hypertension through stimulation of soluble guanylate cyclase. 4 -10 Endogenous CO appears to modulate sinusoidal tone in the hepatic circulation, 11 control the proliferation of vascular smooth muscle cells 12 and suppress the rejection of transplanted hearts. 13 The biological action of heme oxygenase-derived CO is substantiated by the pharmacological effects observed when this gas is applied exogenously to in vitro and in vivo systems. At concentrations ranging from 10 to 500 ppm, CO gas has been reported to mediate potent antiinfl...

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Section: Discussionmentioning

confidence: 99%

Cardioprotective Actions by a Water-Soluble Carbon Monoxide–Releasing Molecule

Clark

Naughton

Shurey

et al. 2003

Circulation Research

623

640

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“…In contrast, good binding affinities were observed if the organometallic moiety was attached at the end of a rigid alkyne chain in the 17 α -position of estradiol derivatives. Molecular modeling studies confirmed that the bulky organometallic group is positioned outside a zone of steric constraint [52] .…”

Section: Hexacarbonyl Dicobalt Complexes As Hormonally Active Compoundsmentioning

confidence: 99%

Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development

Ott

Kircher

Dembiński

et al. 2008

Expert Opinion on Therapeutic Patents

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Background : Organometallic alkyne complexes of the hexacarbonyl dicobalt type (hexacarbonyl[ µ -h 4 -(alkyne)]dicobalt (Co -Co) complexes) are an interesting class of compounds used in modern synthetic chemistry and an increasing number of reports deal also with the use of these complexes in the field of medicinal chemistry. Methods : This review highlights the applications of alkyne hexacarbonyl dicobalt species in biomedical research with a focus on anticancer drug development. Medline, Pubmed, Scifinder and Espacenet internet databases were searched for available literature and patents. Results/conclusion : Preclinical studies on hexacarbonyl dicobalt complexes containing various alkyne (bio)ligands demonstrated a high potential for application (e.g., as antitumor drugs, hormonally active or diagnostic agents). The biological properties of the compounds were mainly determined by the nature of the ligands and the presence of the metal center.

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“…Use of trimethylsulfonium iodide and t-butoxide gives a mixture of two C-17 epimeric epoxides. Attack of nucleophile to the oxirane from the face opens the epoxide ring and gives an estradiol derivative with a side chain at C-17 (2 7,208) (Scheme 11.3) [67,68].…”

Section: Modifications At C-17mentioning

confidence: 80%