Combined Interactions with I1-, I2-Imidazoline Binding Sites and α2-Adrenoceptors To Manage Opioid Addiction

Giusepponi, Maria Elena; Cifani, Carlo; Bonaventura, Maria Vittoria Micioni Di; Mattioli, Laura; Hudson, Alan L.; Diamanti, Eleonora; Bello, Fabio Del; Giannella, Maddalena; Mammoli, Valerio; Paoletti, Corinne Dalila; Piergentili, Alessandro; Pigini, Maria; Quaglia, Wilma

doi:10.1021/acsmedchemlett.6b00290

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…The furyl‐substituted imidazoline 5 f was obtained in 43 % yield. Furthermore, upon variation of the silyl enol ether, imidazolines 5 g – j were obtained in acceptable yields, demonstrating that iron catalysis is useful for the generation of amidinyl radicals and biologically relevant imidazoline motifs …”

Section: Methodsmentioning

confidence: 94%

Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers

Yang

Selander

2017

Chemistry A European J

171

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An iron-catalyzed coupling reaction of O-acyloximes and O-benzoyl amidoximes with silyl enol ethers is reported. The protocol provides access to functionalized pyrroles, 1,6-ketonitriles, pyrrolines and imidazolines via carbon-centered radicals generated from an initially formed iminyl radical. The intramolecular cyclization and ring-opening processes of the iminyl radical take place preferentially over reactions that proceed through a 1,3-hydrogen transfer, providing insights into iron-catalyzed reactions with oxime derivatives. The cheap and environmentally friendly iron catalyst, the broad substrate scope and the functional group compatibility make this protocol useful for synthesis of valuable nitrogen-containing products.

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Section: Methodsmentioning

confidence: 94%

Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers

Yang

Selander

2017

Chemistry A European J

171

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“…Class II includes HDAC4, HDAC5, HDAC6, HDAC7, HDAC9 and HDAC10. SIRTs 1, 2, 3, 4, 5, 6, and 7 belong to class III, and HDAC11 represents class IV [ 12 – 14 ]. It has long been thought that HDACs are responsible for deacetylation of nucleosomal histones solely.…”

Section: Introductionmentioning

confidence: 99%

HDAC8 functions in spindle assembly during mouse oocyte meiosis

Zhang

Jiang

et al. 2017

Oncotarget

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HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments. Consequently, a higher incidence of aneuploidy is generated in HDAC8-depleted MII eggs. In addition, inhibition of HDAC8 activity with its selective inhibitor PCI-34051 phenocopies the spindle/chromosome defects resulting from HDAC8 depletion by siRNA injection. Finally, we find that HDAC8 is required for the correct localization of ϕ-tubulin to spindle poles. Collectively, these data reveal that HDAC8 plays a significant role in regulating spindle assembly and thus ensuring the euploidy in mouse eggs.

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“…Many different pharmacological actions have been associated with imidazoline compounds [21] and our research on them has highlighted that the 2-substituted imidazoline ring linked to an aromatic moiety (Ar) by a biatomic bridge (X) is a bioversatile scaffold to obtain agents interacting with different targets [43][44][45][46] (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

The Use of the Selective Imidazoline I1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity

et al. 2020

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Anti-cancer therapy based on the repeated administration of oxaliplatin is limited by the development of a disabling neuropathic syndrome with detrimental effects on the patient's quality of life. The lack of effective pharmacological approaches calls for the identification of innovative therapeutic strategies based on new targets. We focused our attention on the imidazoline I 1 receptor (I 1 -R) and in particular on the selective I 1 -R agonist 2-(1-([1,1′-biphenyl]-2-yl)propan-2-yl)-4,5-dihydro-1H-imidazole) (carbophenyline). The purpose of this work was the preclinical evaluation of the efficacy of carbophenyline on oxaliplatininduced neuropathic pain in mice. Carbophenyline, acutely per os administered (0.1-10 mg kg −1 ), induced a dose-dependent anti-hyperalgesic effect that was completely blocked by the pre-treatment with the I 1 -R antagonist 3 or the I 1 /α 2 receptor antagonist efaroxan, confirming the I 1 -R-dependent mechanism. Conversely, pre-treatment with the I 2 -R antagonist BU224 did not block the anti-nociceptive effect evoked by carbophenyline. Repeated oral administrations of carbophenyline (1 mg kg −1 ) for 14 days, starting from the first day of oxaliplatin injection, counteracted the development of neuropathic pain in all behavioral tests (cold plate, Von Frey, and paw pressure tests) carried out 24 h after the last carbophenyline treatment on days 7 and 14. In the dorsal horn of the spinal cord, carbophenyline significantly decreased the oxaliplatin-induced astrocyte activation detected by immunofluorescence staining by the specific labelling with GFAP antibody. In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect against oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I 1 -R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain.

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Combined Interactions with I₁-, I₂-Imidazoline Binding Sites and α₂-Adrenoceptors To Manage Opioid Addiction

Cited by 7 publications

References 36 publications

Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers

Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers

HDAC8 functions in spindle assembly during mouse oocyte meiosis

The Use of the Selective Imidazoline I1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity

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