Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain.

ABSTRACT: 1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic^® surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution-alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations.

SUBMITTER: Ioele G

PROVIDER: S-EPMC8070562 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Intramolecular hydrogen bonds in 1,4-dihydropyridine derivatives.

Project description:1,4-Dihydropyridine (1,4-DHP) derivatives have been synthesized and characterized by 1H, 13C, 15N nuclear magnetic resonance (NMR) spectroscopy, secondary proton/deuterium 13C isotope shifts, variable temperature 1H NMR experiments and quantum-chemical calculation. The intramolecular hydrogen bonds NH⋯O=C and CH⋯O=C in these compounds were established by NMR and quantum-chemical studies The downfield shift of the NH proton, accompanied by the upfield shift of the 15N nuclear magnetic resonance signals, the shift to the higher wavenumbers of the NH stretching vibration in the infrared spectra and the increase of the 1J(15N,1H) values may indicate the shortening of the N-H bond length upon intramolecular NH⋯O=C hydrogen bond formation.

| S-EPMC6030305 | biostudies-literature

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists.

Project description:The mineralocorticoid receptor (MR) belongs to the steroid receptor subfamily of nuclear receptors. MR is a transcription factor key in regulating blood pressure and mineral homeostasis. In addition, it plays an important role in a broad range of biological and pathological conditions, greatly expanding its interest as a pharmacological target. Non-steroidal MR antagonists (MRAs) are of particular interest to avoid side effects and achieve tissue-specific modulation of the receptor. The 1,4-dihydropyridine (1,4-DHP) ring has been identified as an appropriate scaffold to develop non-steroidal MRAs. We report the identification of a novel series of 1,4-DHP that has been guided by structure-based drug design, focusing on the less explored DHP position 2. Interestingly, substituents at this position might interfere with MR helix H12 disposition, which is essential for the recruitment of co-regulators. Several of the newly synthesized 1,4-DHPs show interesting properties as MRAs and have a good selectivity profile. These 1,4-DHPs promote MR nuclear translocation with less efficiency than the natural agonist aldosterone, which explains, at least in part, its antagonist character. Molecular dynamic studies are suggestive of several derivatives interfering with the disposition of H12 in the agonist-associated conformation, and thus, they might stabilize an MR conformation unable to recruit co-activators.

| S-EPMC9917360 | biostudies-literature

First Organocatalytic Asymmetric Synthesis of 1-Benzamido-1,4-Dihydropyridine Derivatives.

Project description:Preliminary results concerning the first asymmetric synthesis of highly functionalized 1-benzamido-1,4-dihydropyridine derivatives via the reaction of hydrazones with alkylidenemalononitriles in the presence of ?-isocupreidine catalyst are reported. The moderate, but promising, enantioselectivity observed (40?54% ee), opens the door to a new area of research for the asymmetric construction of new chiral 1,4-dihydropyridine derivatives, whose enantioselective catalytic preparation are still very limited. Moreover, the use of hydrazones for the enantioselective construction of chiral 1,4-dihydropyridines has been overlooked in the literature so far. Therefore, our research represents a pivotal example in this field which remains still unexplored.

| S-EPMC6222298 | biostudies-literature

Intramolecular C-H···O hydrogen bonding in 1,4-dihydropyridine derivatives.

Project description:The diastereotopy of the methylene protons at positions 2 and 6 in 1,4-dihydropiridine derivatives with various substituents has been investigated. NMR spectroscopy and quantum chemistry calculations show that the CH···O intramolecular hydrogen bond is one of the factors amplifying the chemical shift differences in the 1H-NMR spectra.

| S-EPMC6264772 | biostudies-literature

Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC.

Project description:1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological activities between the enantiomers. In the present study, enantioseparation of seventeen DHP structural analogues, consisting of either pharmacologically active or newly synthesized derivatives, (M2-4, MD5, HM2, HM10, CE5, N11, N10, N7, M11, MC6-8, MC13, MD23, and 42IIP) by high-performance liquid chromatography was investigated using immobilized polysaccharide-based chiral stationary phase, Chiralpak IC column. Due to the solvent versatility of the covalently immobilized chiral stationary phase in enantiomer separation, multiple elution modes including standard normal phase, nonstandard mobile phase, and reversed phase were used to expand the possibility to find the optimum enantioselective conditions for the tested analytes. Under appropriate separation conditions, complete enantiomeric separation was obtained for nearly all compounds except MC6-8 and MC13 which contained two chiral centers. Additionally, the effects of the polar modifier, the additive, and column temperature on the chiral recognition were evaluated. The thermodynamic parameters calculated according to the linear van't Hoff equation indicated that the chiral separations in this study were enthalpy-driven or entropy-driven. Some parameters of method validation such as linearity, limit of quantitation, and repeatability were also measured for all studied compounds to prove the reliability of the method.

| S-EPMC6566779 | biostudies-literature

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain.

Project description:Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain.

| S-EPMC7432736 | biostudies-literature

Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer's Disease.

Project description:Alzheimer's disease is a chronic and irreversible pathological process that has become the most prevalent neurodegenerative disease. Currently, it is considered a multifactorial disease where oxidative stress and chronic neuroinflammation play a crucial role in its onset and development. Its characteristic neuronal loss has been related to the formation of neurofibrillary tangles mainly composed by hyperphosphorylated tau protein. Hyperphosphorylation of tau protein is related to the over-activity of GSK-3β, a kinase that participates in several pathological mechanisms including neuroinflammation. Neuronal loss is also related to cytosolic Ca2+ homeostasis dysregulation that triggers apoptosis and free radicals production, contributing to oxidative damage and, finally, neuronal death. Under these premises, we have obtained a new family of 4,7-dihydro-2H-pyrazolo[3-b]pyridines as multitarget directed ligands showing potent antioxidant properties and able to scavenge both oxygen and nitrogen radical species, and also, with anti-inflammatory properties. Further characterization has demonstrated their capacity to inhibit GSK-3β and to block L-type voltage dependent calcium channels. Novel derivatives have also demonstrated an interesting neuroprotective profile on in vitro models of neurodegeneration. Finally, compound 4g revokes cellular death induced by tau hyperphosphorylation in hippocampal slices by blocking reactive oxygen species (ROS) production. In conclusion, the multitarget profile exhibited by these compounds is a novel therapeutic strategy of potential interest in the search of novel treatments for Alzheimer's disease.

| S-EPMC7463999 | biostudies-literature

Green approach for synthesis of bioactive Hantzsch 1,4-dihydropyridine derivatives based on thiophene moiety via multicomponent reaction.

Project description:A novel green and efficient one-pot multicomponent reaction of dihydropyridine derivatives was reported as having good to excellent yield. In the presence of the catalyst ceric ammonium nitrate (CAN), different 1,3-diones and same starting materials as 5-bromothiophene-2-carboxaldehyde and ammonium acetate were used at room temperature under solvent-free condition for the Hantzsch pyridine synthesis within a short period of time. All compounds were evaluated for their in vitro antibacterial and antifungal activity and, interestingly, we found that 5(b-f) show excellent activity compared with Ampicillin, whereas only the 5e compound shows excellent antifungal activity against Candida albicans compared with griseofulvin. The cytotoxicity of all compounds has been assessed against breast tumour cell lines (BT-549), but no activity was found. The X-ray structure of one such compound, 5a, viewed as a colourless block crystal, corresponded accurately to a primitive monoclinic cell.

| S-EPMC5493906 | biostudies-literature

Design of 1,4-Dihydropyridine Hybrid Benzamide Derivatives: Synthesis and Evaluation of Analgesic Activity and Their Molecular Docking Studies.

Project description:PurposeThis study aims to determine the analgesic activity of 1,4-dihydropyridine hybrid benzamide derivatives. These hybrid derivatives were synthesized, and their analgesic activity was studied. The synthesis method applied was a one-step reaction involving a green chemistry approach.MethodsThe compounds were prepared via the amination method with a yield ranging between 82% and 93%. The title compounds were confirmed by means of IR, 1H and 13C NMR, and mass spectral analyses. The pharmacological activity of all the synthesized compounds was evaluated, and the analgesic activities were monitored in vivo (by tail immersion methods), with a digital analgesiometer. The drug response and damage of tail ata concentration of 10 mg/kg were measured by tail-flicking latency.ResultsThe activity of compound 2c (81.35% activity at 5mg/kg) can be correlated with its salicylamidemoiety (13.99% activity at 5mg/kg), and diclofenac showed comparable activity (79.21% activity at 5mg/kg reference drugs). Compound 2c has a higher potential to inhibit COX proteins compared to diclofenac. The drug-like nature of the molecule 2c corresponds to its ADME properties.ConclusionIn this study, all the synthesized compounds were found to possess significant analgesic activities; particularly, the performance of compound 2c is excellent. Thus, the preparative method described is an apt route for developing novel therapeutic formulations.

| S-EPMC9699661 | biostudies-literature

TNT model of neuropathic pain

Project description:In this experiment we compare the effect of tibial nerve transection on gene expression within the dorsal root ganglion (DRG) of rats.

2014-08-01 | E-MTAB-2260 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data