Activities of 2-phthalimidethyl nitrate and 2-phthalimidethanol in the models of nociceptive response and edema induced by formaldehyde in mice and preliminary investigation of the underlying mechanisms

Godin, Adriana M.; Araújo, Débora P.; César, Isabela Costa; Menezes, Raquel R.; Brito, Ana Mercy S.; Melo, Ivo S.F.; Coura, Giovanna M.E.; Bastos, Leandro F.S.; Almeida, Mariana O.; Byrro, Ricardo Martins Duarte; Matsui, Tamires C.; Batista, Carla R.A.; Pianetti, Gérson Antônio; Fátima, Ângelo de; Machado, Renes R.; Coelho, Márcio M.

doi:10.1016/j.ejphar.2015.02.052

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…An interesting group of bioactive molecules is heterocyclic compounds, isoindole derivatives, included in the group of privileged structures [9]. So far, their anti-inflammatory, antibacterial, anticonvulsant, and antifungal properties have been proven [10][11][12]. The definition of the privileged structure describes chemical compounds capable of binding to many biological targets, in line with the principles of modern polypharmacotherapy and current methods of searching for new drugs, which are composed of groups of pharmacophores with an affinity for many different target points of the organism [9].…”

Section: Introductionmentioning

confidence: 99%

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins

Marciniak

Kotynia

Szkatuła

et al. 2022

IJMS

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Many publications in databases deal with the interactions of new drugs with albumin. However, it is not only albumin that is responsible for binding pharmaceutical molecules to proteins in the human body. There are many more proteins in plasma that are important for the study of the ADME pathway. Therefore, in this study, we have shown the results of the interactions between the plasma proteins albumin, orosomucoid, and gamma globulins and non-toxic anti-inflammatory phthalimide analogs, which due to the promising obtained results, may be potential candidates in the group of analgesic and anti-inflammatory drugs. Using spectroscopic methods and molecular modeling, we showed that all four tested compounds form complexes with the analyzed proteins. The formation of a complex with proteins raises the pharmacological efficacy of the drug. Therefore, the obtained results could be a step in the study of the pharmacokinetics and pharmacodynamics of new potential pharmaceuticals.

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Section: Introductionmentioning

confidence: 99%

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins

Marciniak

Kotynia

Szkatuła

et al. 2022

IJMS

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“…It has been proven that the phthalimide ring does not cause the side effects characteristic of glutarimide derivatives, and phthalimides are the basis of many products with proven biological activity, including analgesics, anti-inflammatories, and cholinesterases inhibitors used in Alzheimer’s disease [ 1 , 2 , 3 , 4 , 5 ]. Phthalimide analogs exhibit interesting biological activities, including anticonvulsant, antibacterial, antifungal, anti-inflammatory, and analgesic activities [ 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

Szkatuła

Krzyżak

Stanowska

et al. 2021

IJMS

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Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.

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“…An opioid receptor antagonist (naltrexone, 5 mg/kg; Sigma), α1 adrenoreceptor antagonist (prazosin hydrochloride, 1 mg/kg; Sigma), α2 adrenoreceptor antagonist (yohimbine hydrochloride, 1 mg/kg; Sigma), and 5-HT1/2 receptor antagonist (cyproheptadine hydrochloride, 1 mg/kg; Sigma) were dissolved in saline 87 . While a CB1R antagonist (AM251, 4 mg/kg; Sigma) was dissolved in a solution of Tween-80, ethanol, and saline (1:1:18) 88 , 89 . Additionally, to investigate whether the effects of MCH were mediated via MCH1R, a MCH1R antagonist, TC-MCH 7c (10 mg/kg; Tocris Biosciences) was dissolved in 1% dimethyl sulfoxide (DMSO; Sigma) 90 prior to its administration.…”

Section: Methodsmentioning

confidence: 99%

Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice

Jang

Park

et al. 2018

Sci Rep

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The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH−/− mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly increased mechanical and thermal pain thresholds in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH in both pain models, suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal grey. The MCH1R antagonist abolished the effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.

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Activities of 2-phthalimidethyl nitrate and 2-phthalimidethanol in the models of nociceptive response and edema induced by formaldehyde in mice and preliminary investigation of the underlying mechanisms

Cited by 8 publications

References 44 publications

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins

A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice

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