The Absolute Best Science Experiment for 1-(4-Methoxyphenyl)-1H-pyrrole-2,5-dione

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Characterization in dual activation by oxaliplatin, a platinum-based chemotherapeutic agent of hyperpolarization-activated cation and electroporation-induced currents

Oxaliplatin (OXAL) is regarded as a platinum-based anti-neoplastic agent. However, its perturbations on membrane ionic currents in neurons and neuroendocrine or endocrine cells are largely unclear, though peripheral neuropathy has been noted during its long-term administration. In this study, we investigated how the presence of OXAL and other related compounds can interact with two types of inward currents; namely, hyperpolarization-activated cation current (Ih) and membrane electroporation-induced current (IMEP). OXAL increased the amplitude or activation rate constant of Ih in a concentration-dependent manner with effective EC50 or KD values of 3.2 or 6.4 muM, respectively, in pituitary GH3 cells. The stimulation by this agent of Ih could be attenuated by subsequent addition of ivabradine, protopine, or dexmedetomidine. Cell exposure to OXAL (3 muM) resulted in an approximately 11 mV rightward shift in Ih activation along the voltage axis with minimal changes in the gating charge of the curve. The exposure to OXAL also effected an elevation in area of the voltage-dependent hysteresis elicited by long-lasting triangular ramp. Additionally, its application resulted in an increase in the amplitude of IMEP elicited by large hyperpolarization in GH3 cells with an EC50 value of 1.3 muM. However, in the continued presence of OXAL, further addition of ivabradine, protopine, or dexmedetomidine always resulted in failure to attenuate the OXAL-induced increase of IMEP amplitude effectively. Averaged current-voltage relation of membrane electroporation-induced current (IMEP) was altered in the presence of OXAL. In pituitary R1220 cells, OXAL-stimulated Ih remained effective. In Rolf B1.T olfactory sensory neurons, this agent was also observed to increase IMEP in a concentration-dependent manner. In light of the findings from this study, OXAL-mediated increases of Ih and IMEP may coincide and then synergistically act to increase the amplitude of inward currents, raising the membrane excitability of electrically excitable cells, if similar in vivo findings occur.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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In vitro anti-influenza virus activity of isoquinoline alkaloids from Thalictrum species

The in vitro anti-influenza virus effects of some isoquinoline alkaloids, isolated from Thalictrum species (Ranunculaceae), growing in Mongolia and Sweden have been studied. (-)-thalimonine (Th1) and (-)-thalimonine N-oxide, isolated from the Mongolian plant T. simplex [1 ], [2] inhibited markedly the influenza virus reproduction in vitro; thalictuberine N-oxide was less effective. The synthetic analogues of Th1 [3] as well as the rest of the tested alkaloids, isolated from T. foetidum and T. flavum [4], [5] were not active. At a concentration range between 0.1-6.4 muM Th1 inhibited viral reproduction in a selective and specific way.

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Pyrroline – Wikipedia,
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Cytochrome P450 isoenzymes involved in rat liver microsomal metabolism of californine and protopine

Studies are described on the cytochrome P450 (CYP) isoenzyme dependence of the main metabolic steps of the Eschscholtzia californica alkaloids californine and protopine using rat liver microsomes. Preparations of E. californica are in use as phytopharmaceuticals and as herbal drugs of abuse. CYP isoenyzme dependences were studied using specific chemical inhibitors for CYP1A2, CYP2D1, and CYP3A2 (alpha-naphthoflavone, quinine, and ketoconazole, respectively). CYP2C11 was inhibited by specific antibodies for lack of specific chemical inhibitors. Californine N-demethylation was mainly catalyzed by CYP3A2 and to a minor extent by CYP1A2 and CYP2D1, but not by CYP2C11. CYP2D1 and CYP2C11 were shown to be mainly involved in demethylenation of both, californine and protopine, while CYP1A2 and CYP3A2 showed only minor contribution. Kinetic parameters of the reactions were established. Km and Vmax values for the californine N-demethylation were 4.5¡À4.7 muM and 22.9¡À13.7 min/mg protein (high affinity) and 161.3¡À16.7 muM and 311.8¡À39.4 min/mg protein (low affinity), respectively. Californine demethylenation and protopine demethylenation showed substrate inhibition and Km and Vmax values were 5.0¡À0.5 and 7.1¡À0.6 muM and 83.3¡À2.6 and 160.7¡À4.0 min/mg protein, respectively.

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Pyrroline – Wikipedia,
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Alkaloids of Meconopsis cambrica (L.) Vig. and M. robusta hook. f. et Thoms

Additional alkaloids (+)-roemerine (3b), (+)-corytuberine (3d), (-)-N-methylmecambridinium and alkaloid MC 2 (the last two as iodides) were isolated as minor alkaloidal components from Meconopsis cambrica (L.) VIG. (Papaveraceae) besides of the dominant known alkaloids (-)-mecambrine (1), (-)-mecambridine (2), (-)-flavinantine (4) and (+)-magnoflorine (5), and a small amount of (+)-mecambroline (3a). Minute quantities of protopine, allocryptopine, roemeroline, papaverrubine D and C, berberine, coptisine, corysamine and palmatine were identified by thin layer chromatography (TLC). From M. robusta HOOK. f. et THOMS., protopine, (-)-amurensinine (6) and two incompletely characterized alkaloids MRO 1 and MRO 2 were isolated, and allocryptopine, cryptopine, rhoeadine, 6-methoxy-2-methyl-1,2,3,4-tetrahydro-beta-carboline, alkaloid MR 1, coptisine, corysamine, magnoflorine, corytuberine and N-methylamurensininium salt were detected on TLC.

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Pyrroline – Wikipedia,
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Characterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes

Phytomedicinal preparations containing extracts of the plant Chelidonium majus (Greater Celandine)have been used in the therapy of upper abdominal disorders. C. majus alkaloids (CAL)were suspected to be responsible for reported cases of liver symptoms including cases of acute liver failure in patients upon treatment with certain C. majus preparations. Based on these reports, a safe oral daily dose limit of not more than 2.5 mg CAL was established in the EU. However, C. majus extracts and individual CAL were not able to elicit similar adverse effects when given orally to pigs or rats. We found that CAL differ considerably in their cytotoxicity in rat hepatocytes in culture. The cationic congeners chelerythrine, coptisine and sanguinarine were the most toxic ones (EC20 values ?2 muM)while the neutral congeners chelidonine, dihydrosanguinarine and protopine were less toxic, with a rank order of toxicity of coptisine > chelerythrine > sanguinarine > chelidonine > protopine > dihydrosanguinarine. Calculation of octanol-water partition coefficients revealed that the most cytotoxic CAL in hepatocytes were the cationic polar ones. At cytotoxic concentrations sanguinarine led to a marked decrease in reduced and oxidized intracellular glutathione while the much less cytotoxic dihydrosanguinarine did not. After glutathione depletion with menadione, CAL toxicity was only slightly enhanced. Comparison of the cytotoxic concentrations to reported liver levels in experimental animals suggests that the latter were too low to cause hepatotoxicity, probably due to an extremely low oral availability of certain CAL.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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From protopines to berbines: Synthesis of 1-methoxystylopine and its N-metho salts from coulteropine

The transformation of protopines into berbines under improved conditions has been used to synthesize 1-methoxystylopine. Coulteropine, the main alkaloid from Romneya coulteri, was used as the starting protopine to accomplish the stereocontrolled synthesis of both cis and trans N-methyl-1-methoxystylopinium salts. The results of ab initio calculations (B3LYP/6-31G**) which are consistent with experimental data, sustain the influence of the C-1 substituent on both the conformational equilibrium of berbines and the rate of N-methylation.

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Pyrroline – Wikipedia,
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PROTOPINE-N-OXIDE, AN ALKALOID FROM BOCCONIA CORDATA

The structure of a minor alkaloid of Bocconia cordata has been deduced as protopine-N-oxide by spectroscopic methods and confirmed by synthesis. Key Word Index – Bocconia cordata; Papaveraceae; alkaloids; protopine-N-oxide.

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Factors influencing breath analysis results in patients with diabetes mellitus

Breath analysis is used to detect the composition of exhaled gas. As a quick and non-invasive detection method, breath analysis provides deep insights into the progression of various kinds of diseases, especially those with metabolism disorders. Abundant information on volatile compounds in diabetic patients has been studied in numerous articles in the literature. However, exhaled gas in diabetic patients can be altered by various complications. So far, little attention has been paid to this alteration. In our paper, we found that under air pollution conditions, diabetic patients exhale more nitric oxide. Diabetic patients with heart failure exhale more acetone than those without heart failure. After 13C-labeled glucose intake, patients infected with Helicobacter pylori exhaled more 13Cand less 18O than those without infection. Exhalation with chronic kidney disease changes volatile organic compounds on a large scale. Diabetic patients with ketoacidosis exhale more acetone than those without ketoacidosis. Some specific volatile organic compounds also emanate from diabetic feet. By monitoring breath frequency, diabetic patients with obstructive sleep apnea syndrome exhibit a unique breath pattern and rhythm as compared with other diabetic patients, and sleep apnea is prevalent among diabetic patients. In addition to clinical findings, we analyzed the underlying mechanisms at the levels of molecules, cells and whole bodies, and provided suggestions for further studies.

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Pyrroline – Wikipedia,
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Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1

Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.

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Pyrroline – Wikipedia,
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ALKALOIDS OF SARCOCAPNOS CRASSIFOLIA SUBSP. SPECIOSA

Thirty-four benzylisoquinoline alkaloids were isolated from the aerial parts of Sarcocapnos crassifolia subsp. speciosa.Twenty-seven of them were identified as the following known alkaloids.Benzophenanthridines: 8-hydroxymethyl dihydrosanguinarine, (+)-chelidonine and oxysanguinarine.Ribasines: (+)-ribasine.Aporphinoids: (+)-glaucine, (+)-N-methyl laurotetanine, (+)-isoboldine, O-methyl atheroline and corunnine.Morphinandienones: (-)-pallidine and (+)-salutaridine. 1-Benzylisoquinolines: (+)-crassifoline.Protopines: protopine.Protoberberines: (-)-scoulerine.Cularines and related compounds: (+)-cularine, (+)-cularidine, (+)-celtisine, (+)-breoganine, (+)-sarcocapnidine, (+)-claviculine, oxocularine, oxocompostelline, oxosarcocapnidine, oxosarcophylline, secocularine and secocularidine.Dibenzopyranazepines: (-)-clavizepine.The remainder were seven new cularine-type alkaloids which we named (+)-enneaphylline, (+)-sarcophylline, (+)-norsarcocapnidine, oxocularidine, secosarcocapnidine, norsecocularidine and norsecosarcocapnidine.Their structures have been elucidated by spectroscopic and chemical methods. – Keywords: Sarcocapnos crassifolia subsp. speciosa; Fumariaceae; alkaloid content of aerial parts; 1-benzylisoquinoline alkaloids; novel cularines.

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