Synthesis and Activity of Novel Glutathione Analogues Containing an Urethane Backbone Linkage.

Cacciatore, Ivana; Caccuri, Anna Maria; Stefano, A. Di; Luisi, Grazia; Nalli, Marianna; Pinnen, Francesco; Ricci, Giorgio; Sozio, Piera

doi:10.1002/chin.200404154

Cited by 3 publications

(4 citation statements)

References 1 publication

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“…H-Cys(Allyl)-OBu t (6). A suspension of H-Cys-(Allyl)−OH (4.16 g, 25.8 mmol) in AcOBu t (375 mL) was slowly added to HClO 4 (7.74 mL) at 20 °C.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…A variety of GSH derivatives have been extensively studied to discover therapeutic molecules for the treatment of the above-reported disorders. − Unfortunately, GSH possesses some limitations in its pharmacological use due to its unfavorable pharmacokinetic properties, having a plasmatic half-life lower than 3 min . These disadvantages can be overcome using the prodrug strategy, a medicinal-chemistry-based approach widely used to enhance the delivery features of drugs .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of a Novel Cyclic Prodrug of S-Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells

Patruno¹,

Fornasari²,

Stefano³

et al. 2014

Mol. Pharmaceutics

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A novel cyclic prodrug of S-allyl-glutathione (CP11), obtained by using an acyloxy-alkoxy linker, was estimated for its pharmacokinetic and biological properties. The stability of CP11 was evaluated at pH 1.2, 7.4, in simulated fluids with different concentrations of enzymes, and in human plasma. The anti-inflammatory ability of CP11 was assessed in U937 cells, an immortalized human monocyte cell line. Results showed that CP11 is stable at acidic pH showing a possible advantage for oral delivery due to the longer permanence in the stomach. Having a permeability coefficient of 2.49 × 10(-6) cm s(-1), it was classified as discrete BBB-permeable compound. Biological studies revealed that CP11 is able to modulate inflammation mediated by LPS in U937 cells preventing the increase of ROS intracellular levels through interaction with the MAPK pathway.

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“…H-Cys(Allyl)-OBu t (6). A suspension of H-Cys-(Allyl)−OH (4.16 g, 25.8 mmol) in AcOBu t (375 mL) was slowly added to HClO 4 (7.74 mL) at 20 °C.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of a Novel Cyclic Prodrug of S-Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells

Patruno¹,

Fornasari²,

Stefano³

et al. 2014

Mol. Pharmaceutics

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“…Its analogues, − individual compounds, , and several prodrug molecules − have been proposed as GST-inhibiting strategies. Furthermore, several GSH analogues have been proposed as more specific reversible − and irreversible GST inhibitors, exploiting the high affinity of GSTs for the tripeptide substrate GSH. An alternative concept exploits the susceptibility of GSH conjugates (products of GST catalysis) against the GSH-degrading enzyme γ-glutamyltranspeptidase (γGT).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-N-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1

Koutsoumpli

Dimaki

Thireou³

et al. 2012

J. Med. Chem.

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Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (K(i(9)) = 71 ± 4 μM) at the primary site competitively vs CDNB. Derivative 4 binds (K(i(4)) = 135 ± 27 μM) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure.

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“…Oxidative stress is a general hallmark of major neurodegenerative disorders, leading to neuronal cell dysfunction and progressive death [ 270 ]. Glutathione (GSH), lipoic acid (LA), carnosine, and caffeic acid provide potent antioxidant assistance in counteracting the free radicals produced by the ROS [ 222 , 271 ]. One study revealed that SLNs encapsulating LA can be used for the topical delivery of LA as an antiaging agent [ 272 ], with enhanced stability and hydrophilicity [ 273 ].…”

Section: Applications Of Slns In Cns Disordersmentioning

confidence: 99%

Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB

et al. 2021

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The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

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Synthesis and Activity of Novel Glutathione Analogues Containing an Urethane Backbone Linkage.

Cited by 3 publications

References 1 publication

Synthesis of a Novel Cyclic Prodrug of S-Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells

Synthesis of a Novel Cyclic Prodrug of S-Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells

Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-N-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1

Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB

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