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L Angenot

Publications and source records attributed to L Angenot.

At least 19 recordsLinked to original sources
PubMed2006

Study of the physicochemical properties in aqueous medium and molecular modeling of tagitinin C/cyclodextrin complexes.

The inclusion complexes of tagitinin C with beta-, 2,6-di-O-methyl-beta- and gamma-cyclodextrin (CyD) was investigated in aqueous medium. The stoichiometric ratios and stability constants (K(f)) which describe the extent of formation of the complexes have been determined by UV spectroscopy and direct current tast polarography (DC(tast)), respectively. For each complex, a 1:1 molar ratio was formed in solution and the trend of stability constants was K(f) (2,6-di-O-methyl-beta-CyD)>K(f) (gamma-CyD)>K(f) (beta-CyD). The effect of molecular encapsulation on the photochemical conversion of tagitinin C was evaluated. No significant protection efficacy was noticed with beta- and gamma-CyD for the complexed drug with the respect to the free one. On the other hand, the photochemical conversion rate was slowed in presence of 2,6-di-O-methyl-beta-CyD. Data from (1)H NMR and ROESY experiments provided a clear evidence of formation of inclusion complexes. The lactone, the ester and the unsaturated ketone parts of tagitinin C inserted into the wide rim of the CyDs torus. These experimental results were confirmed by the molecular modeling using semiempirical Austin Model 1 (AM1) method.

Chemical Phenomena↗
PubMed2005

Screening of 14 alkaloids isolated from Haplophyllum A. Juss. for their cytotoxic properties.

Further to a systematic chemotaxonomic study of Uzbek Haplophyllum A. Juss. plants selected on ethnopharmacological data, 14 alkaloids were screened for their cytotoxic properties. As a first selection for interesting compounds, each alkaloid was tested against two human cancer cell lines (HeLa and HCT-116), using WST-1 reagent. Of the 14 alkaloids, 5 were cytotoxic when tested against the HeLa line with an IC50 < 100 microM. These five compounds consisted of three furoquinolines: skimmianine; haplopine and gamma-fagarine and two pyranoquinolones: flindersine and haplamine. Only haplamine was active against the HCT-116 line. The cytotoxic properties of these five alkaloids were further investigated against five additional human cancer cell lines. Their structure-activity relationships will be discussed. Of these five pre-selected alkaloids, only haplamine showed significant cytotoxic activity against all the tested cell lines. This is the first report of the cytotoxic activity of haplamine. Finally, this pyranoquinolone alkaloid was tested here against 14 different cancer cell lines and against normal skin fibroblasts.

Alkaloids↗
PubMed2005

Chemical and biological investigations of a toxic plant from Central Africa, Magnistipula butayei subsp. montana.

Magnistipula butayei subsp. montana (Chrysobalanaceae) is known, in the Great Lakes Region, to possess toxicological properties. In this paper, we investigated the acute toxicity (dose levels 50-1600 mg/kg) of its aqueous extract, administered orally to adult Wistar rats. This study demonstrated that the freeze-dried aqueous extract (5%, w/w) possesses high toxicity. The extract caused hypothermia, neurological disorders, including extensor reflex of maximal convulsive induced-seizures at about 2 h after the administered dose, and death occurred (LD50=370 mg/kg) in a dose dependent manner. Blood parameter evaluation revealed slight variations, but these might not have clinical relevance. Histological examination of internal organs (lungs, liver, heart and kidneys) did not reveal any abnormality in the treated group compared to the control. Therefore, it can be concluded that Magnistipula butayei subsp. montana aqueous extract, given orally, is toxic and that its target is the central nervous system. General phytochemical screening revealed that the plant did not contain significant amounts of products known to be toxic, such as alkaloids or cardioactive glycosides, but only catechic tannins, amino acids, saponins and other aphrogen principles in the three parts of the species (fruit, leave and bark).

Africa, Central↗
PubMed2001

Main glucosidase conversion products of the gluco-alkaloids dolichantoside and palicoside.

The enzymatic glucose cleavage of palicoside revealed the biosynthetic pathway to akagerine, whereas the conversion of dolichantoside led to a new quaternary heteroyohimbine alkaloid named N(b)-methyl-21-beta-hydroxy-mayumbine. The hypothetical models of reactions occurring after the conversion of both substrates are proposed. Dolichantoside and palicoside, as well as Strychnos mellodora stem bark crude ethanol extract, exhibit significant antimycotic activity against human pathogens in presence of specific glucosidase.

Alkaloids↗
PubMed2001

5',6'-dehydroguiachrysine and 5',6'-dehydroguiaflavine, two curarizing quaternary indole alkaloids from the stem bark of Strychnos guianensis.

Two new quaternary indole alkaloids 5',6'-dehydroguiachrysine (1) and 5',6'-dehydroguiaflavine (2) were isolated from Strychnos guianensis stem bark. Their structures were determined by analysis of spectral data. Their inhibitory effects on neuromuscular transmission are also reported and compared to that of other quaternary alkaloids.

Alkaloids↗
PubMed2001

Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja.

A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI(50), 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).

Alkaloids↗
PubMed2001

Reversal of chloroquine and mefloquine resistance in Plasmodium falciparum by the two monoindole alkaloids, icajine and isoretuline.

Eight naturally occurring monoindole alkaloids were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance of a chloroquine-resistant strain of Plasmodium falciparum. None of these indole alkaloids has significant intrinsic antiplasmodial activity (IC(50) > 10 microM or 5 microg/ml). Nevertheless, three alkaloids (icajine, isoretuline and strychnobrasiline) did reverse chloroquine resistance at concentrations between 2.5 and 25 microg/ml (IF of 12.82 for isoretuline on W2 strain). The Interaction Factor (IF) equals 2, < 2, or > 2 for additive, antagonistic or synergistic effects of alkaloids on chloroquine inhibition, respectively. Icajine and isoretuline were also assessed in vitro for their mefloquine potentiating activity on a mefloquine-resistant strain of Plasmodium falciparum. Only icajine proved to be synergistic with mefloquine (IF = 15.38).

Alkaloids↗
PubMed2000

Inhibition of croton oil-induced oedema in mice ear skin by capsular polysaccharides from cyanobacteria.

The anti-inflammatory properties of hydrophilic extracts of the capsular polymers of twelve cyanobacterial strains belonging to the genera Phormidium and Nostoc from marine and terrestrial habitats were tested topically on croton oil-induced oedema in mice ear skin. The screening program identified several strains as producers of anti-inflammatory products (up to 56% inhibition of the oedema). The inhibition response was dose-dependent. The application of trichloroacetic acid-treated extracts reduced the oedema by about 60%. On the other hand, one of the strains enhanced the inflammatory response. Analysis of five of the extracts showed the presence of neutral sugars (from 34.3% to 47.1%, w/w), uronic acids (from 7.1% to 26.7%, w/w) and proteins (from 30.1% to 57.0%, w/w) in the crude polymer. Rhamnose, fucose, arabinose, xylose, mannose, glucose, galactose, galacturonic acid and glucuronic acid were detected as well as sulphate groups (from 9.6% to 21.5%, w/w of sugars). The main components found were glucose and mannose.

Animals↗
PubMed2000

Quaternary indole alkaloids from the stem bark of Strychnos guianensis.

Two new quaternary alkaloids, 9-methoxy-Nb-methylgeissoschizol and guiachrysine together with the known compounds C-alkaloid O, fluorocurine, mavacurine, macusine B and C-profluorocurine, were isolated from Strychnos guianensis stembark. The structures of the compounds were elucidated on the basis of spectroscopic studies.

Alkaloids↗
PubMed2000

New antimalarial and cytotoxic sungucine derivatives from Strychnos icaja roots.

Reinvestigation of Strychnos icaja Baillon resulted in the isolation of vomicine, isostrychnine and of three new sungucine derivatives, named isosungucine (8), 18-hydroxy-sungucine (9) and 18-hydroxy-isosungucine (10). They were identified by detailed spectroscopic methods. The complete 1H- and 13C-NMR study of sungucine was also realized. Some of these compounds were highly active against Plasmodium falciparum in vitro and more particularly against the chloroquine-resistant strain. Compound 10 showed a selective antiplasmodial activity, with > 100-fold greater toxicity towards Plasmodium falciparum, relative to cultured human cancer cells (KB and HeLa lines) or fibroblasts (WI38).

Alkaloids↗
PubMed1999

Anti-inflammatory and immunological effects of Centaurea cyanus flower-heads.

Centaurea cyanus flower-heads are used in European phytotherapy for the treatment of minor ocular inflammations. Different pharmacological experiments (inhibition of carrageenan, zymosan and croton oil-induced oedemas, inhibition of plasma haemolytic activity, induction of anaphylatoxin activity) showed that polysaccharides extracted from C. cyanus flower-heads had anti-inflammatory properties and interfered with complement. Moreover, these polysaccharides were found to be mainly composed of galacturonic acid, arabinose, glucose, rhamnose and galactose.

Anaphylatoxins↗
PubMed1999

Stimulation of topoisomerase II-mediated DNA cleavage by three DNA-intercalating plant alkaloids: cryptolepine, matadine, and serpentine.

Cryptolepine, matadine, and serpentine are three indoloquinoline alkaloids isolated from the roots of African plants: Cryptolepis sanguinolenta, Strychnos gossweileri, and Rauwolfia serpentina, respectively. For a long time, these alkaloids have been used in African folk medicine in the form of plant extracts for the treatment of multiple diseases, in particular as antimalarial drugs. To date, the molecular basis for their diverse biological effects remains poorly understood. To elucidate their mechanism of action, we studied their interaction with DNA and their effects on topoisomerase II. The strength and mode of binding to DNA of the three alkaloids were investigated by spectroscopy. The alkaloids bind tightly to DNA and behave as typical intercalating agents. All three compounds stabilize the topoisomerase II-DNA covalent complex and stimulate the cutting of DNA by topoisomerase II. The poisoning effect is more pronounced with cryptolepine than with matadine and serpentine, but none of the drugs exhibit a preference for cutting at a specific base. Cryptolepine which binds 10-fold more tightly to DNA than the two related alkaloids proves to be much more cytotoxic toward B16 melanoma cells than matadine and serpentine. The cellular consequences of the inhibition of topoisomerase II by cryptolepine were investigated using the HL60 leukemia cell line. The flow cytometry analysis shows that the drug alters the cell cycle distribution, but no sign of drug-induced apoptosis was detected when evaluating the internucleosomal fragmentation of DNA in cells. Cryptolepine-treated cells probably die via necrosis rather than via apoptosis. The results provide evidence that DNA and topoisomerase II are the primary targets of cryptolepine, matadine, and serpentine.

Alkaloids↗
PubMed1999

In vitro activities of strychnos alkaloids and extracts against Plasmodium falciparum.

The in vitro antimalarial activities of 46 alkaloids and extracts from Strychnos species were evaluated. Two types of quasidimeric alkaloids exhibit high and selective activities against Plasmodium. Strychnopentamine and isostrychnopentamine were active against chloroquine-sensitive and -resistant strains (50% inhibitory concentration [IC(50)] approximately 0.15 microM), while dihydrousambarensine exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC(50) = 0.03 microM) than it did against the chloroquine-sensitive strain.

Alkaloids↗
PubMed1998

The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells.

Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host-mediated biological activities, including antibacterial, antiviral, and antimalarial properties. To date, the molecular basis for its diverse biological effects remains largely uncertain. Several lines of evidence strongly suggest that DNA might correspond to its principal cellular target. Consequently, we studied the strength and mode of binding to DNA of cryptolepine by means of absorption, fluorescence, circular, and linear dichroism, as well as by a relaxation assay using DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to reveal that the alkaloid binds tightly to DNA and behaves as a typical intercalating agent. In DNAase I footprinting experiments it was found that the drug interacts preferentially with GC-rich sequences and discriminates against homo-oligomeric runs of A and T. This study has also led to the discovery that cryptolepine is a potent topoisomerase II inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA covalent complexes and stimulates the cutting of DNA at a subset of preexisting topoisomerase II cleavage sites. Taking advantage of the fluorescence of the indoloquinoline chromophore, fluorescence microscopy was used to map cellular uptake of the drug. Cryptolepine easily crosses the cell membranes and accumulates selectively into the nuclei rather than in the cytoplasm of B16 melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is also shown that the alkaloid is more potent at inhibiting DNA synthesis rather than RNA and protein synthesis. Altogether, the results provide direct evidence that DNA is the primary target of cryptolepine and suggest that this alkaloid is a valid candidate for the development of tumor active compounds.

Alkaloids↗
PubMed1997

Characterization of non pigmented B16 melanoma cell-derived cytotoxic factors.

We analyzed and tried to characterize substance(s) responsible for cytotoxic activities detected in culture media conditioned by non pigmented B16 melanoma cells (NPB16). The different cytological tests used showed that ultrafiltrated conditioned media (CM U1 fraction) contained several cytotoxic factors with a Mw lower than 1000 Da. These factors seemed to act either directly or indirectly on cell membranes, mitochondria, on the cell cycle and on protein and DNA synthesis. A cytotoxic activity could be found even after high dilution of CM U1. These cytotoxic factors were rapidly released by B16 cells in culture, independently of cell confluence. Their activities in the treated cells were also very fast and the cytotoxic effects were irreversible after only a few hours of treatment. These factors were not intermediate products during melanogenesis, neither polyamines, nor proteases. At least one of them seemed to be a small acidic and basic stable peptide without disulfide bounds but not heat stable. The synthesis of at least one of these cytotoxic factors was inhibited by cycloheximide and the cytotoxic activity was partially destroyed by pronase and trypsin, but not by pepsin. The cytotoxicity was not modified by copper complexants or free radical inhibitors (bovine serum albumin (BSA), tyrosine, superoxyde dismutase (SOD), catalase, vitamin E). Furthermore the levels of glutathione peroxydase activity and reduced glutathione did not change after treatment by CM U1 as compared to controls.

Animals↗