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FORMATION OF ALKALOIDS IN CORYDALIS OPHIOCARPA CALLUS CULTURE

Corydalis ophiocarpa callus tissue was examined for its isoquinoline alkaloid content.The culture has good biosynthetic capabilities for transformation of exogenous alkaloids.Key Word Index – Corydalis ophiocarpa; Papaveraceae; callus tissue; biotransformation; isoquinoline alkaloids.

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Quantitative measurement of some physico-chemical parameters for the medicinally useful natural products

Lipinski’s rule of five is well received throughout the world and widely used as one of the basic filters to screen ligands for their druggability. In this direction, we have studied 148 biologically active natural products which are available as drugs. Physicochemical parameters such as molecular weight, logP, hydrogen bond donors, hydrogen bond acceptors, number of aromatic rings, molar refractivity and Gibbs free energy were calculated. Statistical results reveal that, they do fall under the Lipinski’s rule of 5 (RO5). The illustration about need for the study, methods followed and results obtained are reported here.

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ALKALOIDS OF Fumaria parviflora

The total alkaloids of the plant Fumaria parviflora Lam., collected in Ashkhabad Province (Turkmen SSR), in the flowering and incipient fruit-bearing period have been studied.The methanolic extraction of 10.5 kg of the plant yielded 0.39percent of total alkaloids, from which cheilanthifoline, scoulerine, parfumine, norjusiphine, isoboldine, coclaurine, dihydrosanguinarine, stylopine, sanguinarine, oxysanguinarine, adlumine, adlumidine, hydrastine, bicuculline, protopine, cryptopine, adlumidiceine, N-methyladlumine, a base with mp 281-282 deg C, and a new alkaloid – d-fumaricine – have been isolated from the plant for the first time.

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A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain

Ethnopharmacological relevance The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents. Materials and methods Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities. Results Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine-antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC50 values of 0.78 mug/mL and 1.29 mug/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells. Conclusions This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.

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Antiplasmodial agents from the Bhutanese medicinal plant Corydalis calliantha

The alkaloidal components of the Bhutanese medicinal plant Corydalis calliantha Long, which is used for the treatment of malaria, have been assessed. Four known alkaloids, protopine (1), scoulerine (2), cheilanthifoline (3) and stylopine (4) are reported from this plant for the fi rst time. The protopine alkaloid, protopine, and the tetrahydroprotoberine alkaloid, cheilanthifoline, showed promising in vitro antiplasmodial activities against Plasmodium falciparum, both wild type (TM4) and multidrug resistant (K1) strains with IC50 values in the range of 2.78-4.29 muM. Such activity had not been demonstrated previously for cheilanthifoline. The results thus support, at a molecular level, the clinical use of this plant in the Bhutanese traditional medicine and identifi ed cheilanthifoline as a potential new antimalarial drug lead. Copyright

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Intracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of chelidonium majus L. By LC-MS/MS

A novel strategy was developed to identify hepatotoxic compounds in traditional Chinese medicines (TCMs). It is based on the exposure of HL-7702 cells to a TCM extract, followed by the identification and further determination of potential hepatotoxic compounds accumulated in the cells by liquid chromatography-tandem mass spectrometry (LC-MS/MS). As a case study, potential hepatotoxic components in Chelidonium majus L. were screened out. Five alkaloids (sanguinarine, coptisine, chelerythrine, protopine, and chelidonine) were identified by LC-MS/MS within 10 min, and their intracellular concentrations were first simultaneously measured by LC-MS/MS with a run time of 4 min. Acell viability assay was performed to assess the cytotoxicity of each alkaloid. With their higher intracellular concentrations, sanguinarine, coptisine, and chelerythrine were identified as the main hepatotoxic constituents in Ch. majus. The study provides a powerful tool for the fast prediction of cytotoxic components in complex natural mixtures on a high-throughput basis.

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ELICITOR INDUCTION AND CHARACTERIZATION OF MICROSOMAL PROTOPINE-6-HYDROXYLASE, THE CENTRAL ENZYME IN BENZOPHENANTHRIDINE ALKALOID BIOSYNTHESIS

The chemical synthesis of <6-3H>protopine is described.Microsomal preparations from Eschscholtzia california cell suspension cultures challenged with a crude elicitor preparation from yeast, catalyse the hydroxylation of <6-3H>protopine with the concomitant formation of <11-3H>dihydrosanguinarine and HO3H.This reaction served as an assay for the enzyme.The hydroxylase reaction is strictly dependent on NADPH as a reducing cofactor and on molecular oxygen.Cytochrome c, inhibitors such as prochloraz and ketoconazole and carbon monoxide inhibit the hydroxylation reaction, suggesting that the enzyme is a cytochrome P-450 linked monooxygenase.The hydroxylase was induced by the yeast elicitor ca eight-fold, 20h after challenging the plant cell culture with the yeast carbohydrate, having no effect on the cell dry weight of the culture.The hydroxylase is specifically present in different plant species that produce benzophenanthridine alkaloids in culture and also respond to induction by the elicitor.

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Chelidonium majus L.: Components with in vitro Affinity for the GABAA Receptor. Positive Cooperation of Alkaloids

The influence of an ethanolic dry extract of Chelidonii herba on the GABAA receptor has been studied in vitro. In the presence of 90 mug/assay a positive cooperation was induced for [3H]muscimol accompanied by an increase of the specific binding (115%) while 160 mug/assay exerted a 50% inhibition of the specific binding of the radioligand [3H]muscimol. The quantitative determination of the Chelidonium alkaloids by HPLC together with the evaluation of the radioreceptor assays of the pure alkaloids revealed that the allosteric modulation of the GABAA receptor is mainly due to protopine. The small amounts of allocryptopine and stylopine assumingly support the action of protopine. Protopine, stylopine, and allocryptopine do not influence the specific binding of [3H]flunitrazepam. Thus, the positive cooperative modulation of the GABAA receptor is not based on an interaction of these alkaloids with the benzodiazepine receptor. The specific [3H]muscimol binding was inhibited only by chelerythrine and sanguinarine with IC50 values of 25 muM and 39 muM, respectively. The content of chelerythrine and sanguinarine in the ethanolic dry extract of Chelidonii herba is 500 or even 1000 times too low to account for the observed interference with the GABAA receptor activity. Thus, the alkaloids are not responsible for the inhibitory action on the GABAA receptor at higher concentrations of the ethanolic dry extract.

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ALKALOIDS FROM Papaver litwinowii FEDDE ex BORNM.

From Papaver litwinowii FEDDE ex BORNM. aporheine ((+)-roemerine) was isolated as the dominant alkaloid in addition to minor alkaloids aporheine methohydroxide, corytuberine, hordenine, (-)-mecambrine, cryptopine, protopine and coptisine.The presence of small amounts of allocryptopine, corydine, isocorydine, scoulerine, corysamine and papaverrubine A, C, D and traces of E(?) was also proved.Corytuberine was now isolated from P. dubium L. as well.

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Application In Synthesis of 1-(4-Methoxyphenyl)-1H-pyrrole-2,5-dione, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 1081-17-0, name is 1-(4-Methoxyphenyl)-1H-pyrrole-2,5-dione. In an article£¬Which mentioned a new discovery about 1081-17-0

ALKALOIDS OF THE TWO Hypecoum L. SPECIES

Alkaloids from Hypecoum procumbens L. and H. leptocarpum HOOK.F. et THOMS. were investigated.Protopine was the dominant alkaloid in both species.From H. procumbens chelerythrine and corydine were newly isolated in addition to the earlier detected alkaloids allocryptopine, sanguinarine, coptisine, and isocorydine.From H. leptocarpum allocryptopine, isocorydine, and corydine were isolated for the first time, in addition to the earlier described alkaloids protopine, sanguinarine, chelerythrine, and coptisine.Cryptopine was detected chromatographically.From the fraction of strongly polar alkaloids of both species magnoflorine, (-)-trans-N-methylstylopinium hydroxide, and in small amounts a new secoberbine alkaloid of oxohypecorinine structure, procumbine (I), and two further alkaloids of unresolved structure were isolated in the form of iodides.

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