Day: November 30, 2022

Ponnusamy, Parasuraman published the artcileMolecular modeling and molecular docking studies on the derivatives of 1,4-dihydropyridine towards Cytochrome P450 for structure based drug design, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is dihydropyridine14 cytochromeP450 cardioprotective agent cardiovascular disease.

Protein-ligand interactions are instrumental for the structure based drug design in the human health care systems to cure problematic diseases especially cardiovascular diseases. To treat the cardiovascular disease, the Calcium Channel Blockers (CCBs) such as 1,4-dihydropyridine (DHP) derivatives have been used in a effective way. In this study, the series of nine DHP derivatives (DHP I-DHP IX) have been docked in the binding pocket of Cytochrome P 450. Among these nine DHP-P 450 complexes, the DHP-III [N-(4-methoxy phenyl)-3,5 dicarbethoxy-2,6-dimethyl-4-(3-nitro phenyl)-1,4-Dihydropyridine] and DHP-VI [2,6-Dimethyl-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid di-Et ester] exhibits lowest binding energy of -11.89 and -11.14 kcal/mol resp., which indicates that these two mols. strongly bind to the binding pocket amino acid residues of P 450 when compared with the other DHP derivatives An anal. of hydrogen bonding interactions shows that Arg212 is essential for high affinity ligand binding. Subsequently, the C(8) atom in the DHPIII-P 450 complex forms strong hydrophobic interaction with Ala3l0 while the C(8) atom in the DHPVI-P 450 complex makes strong hydrogen bonding interaction with Arg212. Comparatively, the C(8) atom was not interacting with neighboring amino acids in other DHP – P 450 complexes. Further, in the DHPIII-P 450 complex, the ligand makes more hydrophobic interactions with the amino acids of Ala370, Phe304, Phe213, Ile369, Met371 and Ser119. The DHP-VI mol. forms strong hydrogen bonding interactions with P 450 whereas in the amlodipine-P 450 complex, amlodipine reduces the better chance of making hydrogen bonding interactions due to the absence of N-Ph ring. Thus the binding of two DHP derivatives such as DHP-III and DHP-VI are found to be higher and exhibit increased binding affinities towards Cytochrome P 450. These two mols. may be considered as a drug candidate for the treatment of cardio vascular diseases as well as in vivo and in vitro studies in future.

Materials Today: Proceedings published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pang, Yefei published the artcileRole of mPRα (PAQR7) in progesterone-induced Ca2+ decrease in human vascular smooth muscle cells, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is progesterone mPRalpha PAQR7 umbilical artery vascular smooth muscle cell; VSMC; calcium; mPRα; signaling.

We have shown progesterone exerts a direct action on vascular smooth muscle cells (VSMCs) to induce relaxation through activation of membrane progesterone receptor alpha (mPRα)-dependent signaling pathways, but information on downstream events is lacking. Progesterone-induced changes in calcium concentrations in human umbilical artery VSMCs through mPRα-dependent signaling pathways and the involvement of Rho/ROCK signaling were investigated. Acute in vitro treatment with progesterone and the selective mPRα agonist 10-ethenyl-19-norprogesterone (Org OD 02-0, 02-0) blocked the rapid prostaglandin F2α-induced calcium increase. This inhibitory progesterone action was prevented by knockdown of mPRα but not by knockdown of the nuclear progesterone receptor, confirming it is mediated through mPRα. The decrease in calcium levels and VSMC relaxation were abolished by treatment with FPL64176 (Ca2+ channel activator), supporting a role for decreased calcium channel activity in this progesterone action. The reduction in calcium was attenuated by pretreatment with pertussis toxin, 8-Bromo-cAMP and forskolin, indicating this progesterone action involves activation of an inhibitory G protein and downregulation of cAMP-dependent signaling. Inhibition of MAPK and Akt signaling with PD98059 and ML-9, resp., prevented the progesteroneinduced calcium concentration decrease and VSMC relaxation. Forskolin decreased progesterone-induced MAPK and Akt phosphorylation which suggests that the cAMP status influences calcium levels indirectly through altering these signaling pathways. Progesterone and 02-0 treatments decreased RhoA activity and ROCK phosphorylation, which suggests that reduced RhoA/ROCK signaling is a component of the mPRα-mediated progesterone actions on VSMCs. The results suggest that progesterone induces VSMC relaxation by reducing cellular calcium levels through mPRα-induced alterations in multiple signaling pathways.

Journal of Molecular Endocrinology published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gonzalez-Montelongo, Maria del Carmen published the artcileNeuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Neuropeptide Y P2X1 Suramin vasoconstriction NF449 Calcium channel; Calcium channel; Neurogenic; Neuropeptide Y; P2X receptors; Vasoconstriction.

Investigate effect of NPY on P2X1-dependent vasoconstriction in mesenteric arteries. Suramin or P2X1 antagonist NF449 abolished α,β-meATP evoked vasoconstrictions. Y1 receptor inhibition (BIBO3304) reversed NPY facilitation of α,β-meATP-evoked vasoconstriction. L-type Ca2+ channel antagonism (nifedipine) had no effect on α,β-meATP-evoked vasoconstrictions, but completely reversed NPY. Elec. field stimulation evoked sympathetic neurogenic vasoconstriction. Neurogenic responses dependent upon dual α1-adrenergic (prazosin) and P2X1 (NF449) receptor activation. Y1 receptor antagonism reduced neurogenic vasoconstriction. Isolation of P2X1 component by α1-adrenergic blockade faciliatory effects of Y1 receptor activation explored. Y1 receptor antagonism reduced P2X1 receptor component during neurogenic vasoconstriction. α1-adrenergic and P2X1 receptors post-junctional receptors during sympathetic neurogenic vasoconstriction in mesenteric arteries. Identified that NPY lacks direct vasoconstrictor effect in mesenteric arteries but can vasoconstriction by enhancing activity of P2X1, activation by exogenous agonists or during sympathetic nerve stimulation. Mechanism of P2X1 facilitation by NPY involved activation of NPY Y1 receptor and L-type Ca2+ channel.

Vascular Pharmacology published new progress about Adrenoceptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Micucci, Matteo published the artcileNeutral/negative α1-AR antagonists and calcium channel blockers at comparison in functional tests on guinea-pig smooth muscle and myocardium, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is smooth muscle myocardium left atrium benzodioxane alpha1 AR antagonist; Calcium channel blockers; Inverse agonism; WB4101; alpha1-antagonists.

In the present exptl. approach, we compared the activity of three calcium channel blockers (nifedipine, diltiazem and verapamil) and of three potent benzodioxane-based α1-AR antagonists, differing for subtype selectivity and inverse agonist properties, in producing smooth muscle relaxation and neg. inotropy under the same test conditions. We selected, as benzodioxane derivatives, (S)-WB4101, inverse agonist with slight α1A/α1B-α1D AR selectivity, and two previously developed analogs. Both of these are potent antagonists at α1D-AR, that is the α1- AR subtype suspected of the highest susceptibility to inverse agonists for its high degree of basal activity, but only one is inverse agonist. We found that all the three benzodioxane-related α1-AR antagonists have significant intrinsic relaxant activity on non-vascular smooth muscle and moderate neg. inotropic effect, while they do not relax aorta. Their potency is always lower than that of three calcium channel blockers. Intrinsic myorelaxant and neg. inotropic activity of the three benzodioxane-based α1-AR antagonist is related neither to a particular profile of α1-AR subtype selectivity nor to whether or not being an inverse agonist, but it parallels the calcium antagonists effects indicating a direct interaction of the three α1-AR antagonists with L-type Ca2+ channels.

Pharmacological Reports published new progress about Adrenoceptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lang, Richard J. published the artcilePacemaker mechanisms driving pyeloureteric peristalsis: modulatory role of interstitial cells, HPLC of Formula: 21829-25-4, the main research area is review calcium cationic channel smooth muscle peristaltic pressure pacemaker; Atypical smooth muscle cells; Calcium channels; Calcium imaging; Interstitial cells; Pacemaking; Pyeloureteric peristalsis; Upper urinary tract.

The peristaltic pressure waves in the renal pelvis that propel urine expressed by the kidney into the ureter towards the bladder have long been considered to be ‘myogenic’, being little affected by blockers of nerve conduction or autonomic neurotransmission, but sustained by the intrinsic release of prostaglandins and sensory neurotransmitters. In uni-papilla mammals, the funnel-shaped renal pelvis consists of a lumen-forming urothelium and a stromal layer enveloped by a plexus of ‘typical’ smooth muscle cells (TSMCs), in multi-papillae kidneys a number of minor and major calyces fuse into a large renal pelvis. Electron microscopic, electrophysiol. and Ca2+ imaging studies have established that the pacemaker cells driving pyeloureteric peristalsis are likely to be morphol. distinct ‘atypical’ smooth muscle cells (ASMCs) that fire Ca2+ transients and spontaneous transient depolarizations (STDs) which trigger propagating nifedipine-sensitive action potentials and Ca2+ waves in the TSMC layer. In uni-calyceal kidneys, ASMCs predominately locate on the serosal surface of the proximal renal pelvis while in multi-papillae kidneys they locate within the sub-urothelial space. ‘Fibroblast-like’ interstitial cells (ICs) located in the sub-urothelial space or adventitia are a mixed population of cells, having regional and species-dependent expression of various Cl-, K+, Ca2+ and cationic channels. ICs display asynchronous Ca2+ transients that periodically synchronize into bursts that accelerate ASMC Ca2+ transient firing. This review presents current knowledge of the architecture of the proximal renal pelvis, the role Ca2+ plays in renal pelvis peristalsis and the mechanisms by which ICs may sustain/accelerate ASMC pacemaking.

Advances in Experimental Medicine and Biology published new progress about Prostaglandins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Furini, Cristiane R. G. published the artcileMolecular Mechanisms in Hippocampus Involved on Object Recognition Memory Consolidation and Reconsolidation, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is hippocampus memory synaptic protein BDNF; AMPA receptors; BDNF; CaMKII; L-VDCCs calcium channels; ORM consolidation; ORM reconsolidation.

Acquired information is stabilized into long-term memory through a process known as consolidation. Though, after consolidation, when stored information is retrieved they can susceptible, allowing modification, updating, strengthening and re-stabilized a new process referred to as memory reconsolidation. Also, considering that the study of link between synaptic proteins is key to understanding of memory processes, we investigated, in male Wistar rats, mol. mechanisms in the hippocampus involved on ORM consolidation and reconsolidation. We verified that the blockade of AMPAr and L-VDCCs calcium channels impaired ORM consolidation and reconsolidation when administered into CA1 immediately after sample phase or reactivation phase and that these impairments were blocked by the administration of AMPAr agonist and of neurotrophin BDNF. Also, the blockade of CaMKII impaired ORM consolidation when administered 3 h after sample phase but had no effect on ORM reconsolidation and its effect was blocked by the administration of BDNF, but not of AMPAr agonist. So, this study provides new evidence of the mol. mechanisms involved on the consolidation and reconsolidation of ORM, demonstrating that AMPAr and L-VDCCs are necessary for the consolidation and reconsolidation of ORM while CaMKII is necessary only for the consolidation and also that there is a link between BDNF and AMPAr, L-VDCCs and CaMKII as well as a link between AMPAr and L-VDCCs on ORM consolidation and reconsolidation.

Neuroscience (Amsterdam, Netherlands) published new progress about AMPA receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ghirardini, Elsa published the artcileMutant prion proteins increase calcium permeability of AMPA receptors, exacerbating excitotoxicity, Quality Control of 21829-25-4, the main research area is prion protein calcium AMPA receptor mutation excitotoxicity.

Prion protein (PrP) mutations are linked to genetic prion diseases, a class of phenotypically heterogeneous neurodegenerative disorders with invariably fatal outcome. How mutant PrP triggers neurodegeneration is not known. Synaptic dysfunction precedes neuronal loss but it is not clear whether, and through which mechanisms, disruption of synaptic activity ultimately leads to neuronal death. Here we show that mutant PrP impairs the secretory trafficking of AMPA receptors (AMPARs). Specifically, intracellular retention of the GluA2 subunit results in synaptic exposure of GluA2-lacking, calcium-permeable AMPARs, leading to increased calcium permeability and enhanced sensitivity to excitotoxic cell death. Mutant PrPs linked to different genetic prion diseases affect AMPAR trafficking and function in different ways. Our findings identify AMPARs as pathogenic targets in genetic prion diseases, and support the involvement of excitotoxicity in neurodegeneration. They also suggest a mechanistic explanation for how different mutant PrPs may cause distinct disease phenotypes.

PLoS Pathogens published new progress about AMPA receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Itsumi, Momoe published the artcileHigh-throughput screen identifies 5-HT receptor as a modulator of AR and a therapeutic target for prostate cancer, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is antitumor AR modulator 5HT receptor therapeutic target prostate cancer; 5-hydroxytryptamine receptor; androgen receptor; high-throughput screen; prostate cancer; protein kinase A.

Background : Eradication of persistent androgen receptor (AR) activity in castration-resistant prostate cancer may be a promising strategy to overcome castration resistance. We aimed to identify novel compounds that inhibit AR activity and could be potential therapeutic agents for prostate cancer. Methods : A high-throughput screening system involving cell lines stably expressing AR protein and AR-responsive luciferase was employed for the 1260 compound library. Mol. and antitumor effects on candidate pathways that interacted with AR signaling were examined in prostate cancer cells expressing AR. Results : The high-throughput screening identified various potential compounds that interfered with AR signaling through known and novel pathways. Among them, a 5-hydroxytryptamine 5A (5-HT5A) receptor antagonist suppressed AR activity through protein kinase A signaling, which was confirmed by 5-HT5A receptor knockdown. Consistently, 5-HT5A receptor inhibitors showed cytotoxic effects toward prostate cancer cells. Conclusions : Taken together, this study identifies 5-HT5A receptor as a promising therapeutic target for prostate cancer via its interaction with AR signaling.

Prostate (Hoboken, NJ, United States) published new progress about 5-HT receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Choe, So-Hui published the artcileEffect of nifedipine, a calcium channel blocker, on the generation of nitric oxide and interleukin-1β by murine macrophages activated by lipopolysaccharide from Prevotella intermedia, Related Products of pyridine-derivatives, the main research area is calcium blockeron nitric oxide interleukin 1 beta lipopolysaccharide; Interleukin-1β; Lipopolysaccharide; Nifedipine; Nitric oxide; Periodontal disease.

The current study was undertaken to explore the influence of nifedipine on the generation of proinflammatory mediators by murine macrophages activated by lipopolysaccharide (LPS) prepared from Prevotella intermedia, a putative periodontal pathogen, and associated mechanisms of action as well. Real-time PCR and immunoblotting were conducted to quantify mRNA and protein expression, resp. NF-κB-dependent secreted embryonic alk. phosphatase (SEAP) levels were estimated by reporter assay. Nifedipine markedly suppressed the generation of iNOS-derived NO and IL-1β together with their mRNA expressions in murine macrophages activated by P. intermedia LPS. LPS-stimulated cells exposed to nifedipine notably increased the mRNA levels of Arg-1, Ym-1, FIZZ1, and TGF-β, which are typical markers for M2 macrophage polarization. Nifedipine induced HO-1 at both gene and protein levels in cells challenged with P. intermedia LPS, and the nifedipine-mediated inhibition of NO generation was significantly abrogated by adding SnPP, an HO-1 inhibitor. Nifedipine inhibited LPS-evoked generation of NO and IL-1β in a PPAR-γ-independent manner. Nifedipine is an inhibitor of P. intermedia LPS-evoked production of NO and IL-1β in murine macrophages and encourages macrophage polarization toward the M2 phenotype. Nifedipine possibly has potential to be used for host modulation of periodontal disease and is worth being further researched.

Naunyn-Schmiedeberg’s Archives of Pharmacology published new progress about Antigens, LyM-1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kumar, Banjara Santosh published the artcileCombined anticonvulsant effect of nifedipine and pentazocine in experimentally induced seizures by maximal electro shock method in mice, HPLC of Formula: 21829-25-4, the main research area is pentazocine nifedipine anticonvulsant combination therapy seizure.

Objective: The aim of the study was to determine the combined anticonvulsant effect of nifedipine (calcium channel blocker) and pentazocine (opioid analgesic) in exptl. induced seizures by Maximal Electro-Shock (MES) method in mice. Methodol.: The swiss albino mice weighing 20-40g of either sex were obtained from National Institute of Nutrition, Hyderabad after obtaining ethical approval. The pretreated mice are subjected to MES stimulation by electro convulsometer with alternate current at intensity required to produce tonic hind limb extension response. The animals showing pos. response are divided into four groups (6 animals per group). Group I received distilled water, group II treated with nifidipine (10mg/kg/bw), group III pentazocine (30mg/kg/bw) and group IV combination of nifidipine (10mg/kg/bw) and pentazocine (30mg/kg/bw). I.p. is the route of administration. The parameters like duration of convulsions, Tonic Hind Limb Extension (THLE) and duration of recovery recorded. P<0.05 was considered as significant and P<0.001 was considered as highly significant. Results: The duration of convulsions, duration of THLE and duration of recovery has been significantly reduced in combination treatment wih nifedipine 10mg/kg and pentazocine 30mg/kg compared to nifedipine 10mg/kg and pentazocine 30mg/kg individually. Conclusion: The results obtained in this study provide supporting pharmacol. evidence of efficacy, possible potential benefit of combining nifedipine with pentazocine in the treatment of epilepsy. Journal of Drug Delivery and Therapeutics published new progress about Anticonvulsants Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem