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A Cavé

Publications and source records attributed to A Cavé.

At least 37 records · Page 2Linked to original sources
PubMed1994

The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmania donovani.

Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the antileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I), 2-n-propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0.54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0.54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-infected mice suppressed parasite burdens in liver by 87.8 and 99.9%, respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.

Alkaloids↗
PubMed1993

Symmetrical rearrangement of the cation-binding sites of parvalbumin upon Ca2+/Mg2+ exchange. A study by 1H 2D NMR.

Two forms of parvalbumin, i.e., the fully Ca-loaded form PaCa2 and the fully Mg-loaded form PaMg2, are investigated by 2D 1H NMR in solution. A detailed analysis of the resonances, which belong to residues involved in direct coordination of Ca2+ and Mg2+, establishes that the sixth ligand, a highly conserved Glu residue at the relative position 12 in both cation-binding sites CD and EF, undergoes a conformational rearrangement through a 120 degrees rotation of its side chain about the C alpha-C beta bond with PaMg2 adopting the less energetically favored g- conformation, as inferred from scalar coupling constants and dipole-dipole contacts measured on the COSY and NOESY spectra, respectively. Similarly, chemical shift effects, which selectively involve NH and C alpha H resonances (as well as side-chain resonances) in both CD and EF sites, point to a symmetrical behavior of both cation-binding sites upon Ca2+/Mg2+ exchange.

Animals↗
PubMed1993

2-substituted quinoline alkaloids as potential antileishmanial drugs.

Ten 2-substituted quinoline alkaloids isolated from a plant used for treatment of New World cutaneous leishmaniasis have antileishmanial in vitro activities against the extracellular forms of Leishmania spp. BALB/c mice infected with Leishmania amazonensis PH8 or H-142 or Leishmania venezuelensis were treated 1 day after the parasitic infection with a quinoline alkaloid (100 mg/kg of body weight per day) or with reference drug N-methylglucamine antimonate (Glucantime) (56 mg of pentavalent antimony [Sbv] per kg per day) for 14 days. Lesion development was the criterium used to assess disease severity. Two three-carbon chain quinolines [2-n-propylquinoline and 2-(1',2'-trans-epoxypropyl)quinoline (chimanine D)] were more potent than N-methylglucamine antimonate against L. amazonensis PH8, and five quinoline alkaloids [2-(3,4-methylenedioxyphenylethyl)quinoline, cusparine, 2-(3,4-dimethoxyphenylethyl)quinoline, 2-(E)-prop-1'-enylquinoline (chimanine B), and skimmianine] were as effective as the reference drug. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 2-n-propylquinoline or chimanine B reduced the severity of lesions but less notably than N-methylglucamine antimonate. 2-n-Propylquinoline exhibited significant activity against the virulent strain L. venezuelensis. The active products did not show any apparent toxicities during the experiment. This study is, to our knowledge, the first to show the activity of 2-substituted quinoline alkaloids for experimental treatment of New World cutaneous leishmaniasis. Further investigations of these compounds might yet prove helpful for the development of new antileishmanial drugs.

Alkaloids↗
PubMed1992

Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis.

The stem barks of Pera benensis are employed by the Chimane Indians in the Bolivian Amazonia as treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. The chloroform extracts containing quinones were found active against the promastigote forms of Leishmania and the epimastigote forms of Trypanosoma cruzi at 10 micrograms ml-1. The activity guided fractionation of the extract by chromatography afforded active compounds. Their structures were elucidated, by spectral and chemical studies, as known naphthoquinones, plumbagin, 3,3'-biplumbagin, 8-8'-biplumbagin, and triterpene, lupeol. The activity in vitro of each compound was evaluated against 5 strains of Leishmania (promastigote), 6 strains of Trypanosoma cruzi (epimastigote) and the intracellular form (amastigote) of Leishmania amazonensis. The baseline drugs used were Glucantime and pentamidine (Leishmania spp.), nifurtimox and benznidazole (T. cruzi). Plumbagin was the most active compound in vitro. This study has demonstrated that Pera benensis, a medicinal plant used in folk medicine, is an efficient treatment of cutaneous leishmaniasis.

Animals↗
PubMed1992

Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis.

Plumbagin, 3,3'-biplumbagin and 8,8'-biplumbagin are naphthoquinones isolated by activity-directed fractionation from a Bolivian plant, Pera benensis, used in folk medicine as treatment of cutaneous leishmaniasis caused by Leishmania braziliensis. BALB/c mice were infected with L. mexicana or L. venezuelensis and treated 24 h after the parasitic infection with plumbagin (5 or 2.5 mg/kg/day), 3,3'-biplumbagin, 8,8'-biplumbagin (25 mg/kg/d) or Glucantime (200 mg/kg/d). Lesion development was the criteria employed to evaluate the inhibitory effect. The bis-naphthoquinones were less potent than Glucantime against L. amazonensis and L. venezuelensis. Plubagin and Glucantime delayed the development of L. amazonensis and L. venezuelensis. Assays of a single local treatment on foot-pad infection two weeks after the parasitic inoculation with L. amazonensis showed that 8,8'-biplumbagin (50 mg/kg/d) was as potent as Glucantime (400 mg/kg/d).

Animals↗
PubMed1991

Antiparasitic activity of Annona muricata and Annona cherimolia seeds.

Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antiparasitic activity against E. histolytica, N. brasiliensis, M. dessetae and A. salina. The acetogenins isolated from these extracts are found to be responsible for the important activity on infective larvae of Molinema desetae.

Animals↗
PubMed1988

Two-dimensional 1H nuclear magnetic resonance study of pike pI 5.0 parvalbumin (Esox lucius). Sequential resonance assignments and folding of the polypeptide chain.

The structure of alpha pike 5.0 parvalbumin under its Ca-loaded form (or PaCa2) is studied in solution by two-dimensional 1H nuclear magnetic resonance (n.m.r.) at 360 MHz using a conventional strategy of sequential assignments, which involved correlated spectroscopy, relayed coherence transfer spectroscopy and nuclear Overhauser enhancement spectroscopy. In order to overcome the problem of spectral overlapping due to the presence of 108 residues in the protein, experiments were performed at different pH and temperature values, either in 1H2O or in 2H2O solutions. The amino acid sequence of pike 5.0 parvalbumin is thus fully characterized by nearly the totality of its NH, C alpha H and C beta H resonances originating from the different residues (421 protons assigned among 429 in total). When associated with the remaining side resonances, these sequence-specific assignments provide a basis for establishing the secondary organization and tertiary folding of the polypeptide chain. Pike 5.0 parvalbumin was selected as a characteristic representative of the alpha phylogenic series, for which no crystalline structure is presently available, in contrast with the beta series for which two crystalline structures have been determined. A parvalbumin molecule with a single polypeptide chain of 108 amino acids represents one of the highest molecular weights analyzed so far by two-dimensional n.m.r. spectroscopy. The use of a moderate magnetic field strength, with 1H nuclei resonating at 360 MHz, is justified by the fact that ring current effects are operating favorably in this globular protein with a high phenylalanine content. A three-dimensional structure has been generated by the "distance geometry" or DISGEO computational procedure on the basis of about 450 interproton nuclear Overhauser enhancement connectives (short, medium and long-range) in conjunction with a selection of phi and chi dihedral angle constraints. The coherence of the calculated structure, which displays all the features of the typical folding of a parvalbumin protein, provides a good test of reliability of the n.m.r. data collected so far. Although similar to a beta parvalbumin in the folding of its polypeptide chain, the alpha parvalbumin studied here differs markedly from a beta parvalbumin in the length of its C-terminal F-helix domain, which includes 11 residues instead of ten in the latter.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1988

[ Active trypanocidal alkaloids, bisbenzylisoquinoles ii. active in vitro against trypanosoma cruzi the agent responsible for trypanosomiasis, south america].

Chagas disease caused by the protozoan Trypanosoma cruzi is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Trypanosoma cruzi (imidazol compounds, lampit and benznidazol) are not very convenient products. Since it is known that protozoan Trypanosoma are close to Leishmania we studied the action of 14 bisbenzylisoquinoline alkaloids, in vitro, on three strains of T. cruzi (Tulahuen, C8C11, and 1979 CL1). As in the case of Leishmania, gyrocarpine, daphnandrine and obaberine showed an interesting activity and we judge them to be worthy of in vivo assays.

Alkaloids↗
PubMed1986

Metal ion binding to parvalbumin. A proton NMR study.

The 1H NMR spectra of carp parvalbumin saturated with Ca2+, Cd2+, La3+ and Lu3+ were compared, using 2D 1H NMR techniques as well as conventional 1H NMR spectra. The Ca2+ and Cd2+ saturated parvalbumin (with both high affinity Ca2+-binding sites occupied) gave rise to very similar spectra. This shows that these two species have almost identical protein conformations. The 1H NMR spectrum from the Ln3+ saturated parvalbumins deviated from the other two and it was therefore concluded that Cd2+ is a better probe for Ca2+ than Ln3+ in parvalbumin and probably also for related calcium binding proteins. The addition of excess of divalent metal ions, such as Mg2+ or Ca2+, causes small changes in the chemical shift of some methyl resonances. This is presumably caused by binding of these metal ions to a third site close to the CD site which is made up of the carboxylic groups from Glu 60 and Asp 61.

Animals↗
PubMed1985

Metal-ion binding to parvalbumin. A 113Cd-n.m.r. study of the binding of different lanthanide ions.

113Cd-n.m.r. studies were used to investigate the binding of the lanthanide ions La3+, Gd3+, Tb3+, Yb3+ and Lu3+ to parvalbumins. It was shown that lanthanide ions with a smaller ionic radius bind sequentially to Cd2+-saturated parvalbumin, whereas those with a larger ionic radius bind with similar affinity to both the CD site and the EF site. The smallest ion, Lu3+, does in fact not compete significantly with Cd2+ for the CD site in carp parvalbumin, but appears to bind only to the EF site. This preference of the smaller lanthanide ions for the EF site was used to assign the n.m.r. signals for protein-bound 113Cd. By using Cd n.m.r. and Tb3+ fluorescence it was also shown for alpha-lineage parvalbumin from pike that these proteins possess a third site that can bind lanthanide ions. This site is, however, much weaker than in the beta-lineage parvalbumins. It was used to assign the 113Cd resonances from protein-bound Cd2+ ions in the spectrum of pike pI5.0 parvalbumin.

Animals↗
PubMed1982

NMR studies on parvalbumin phylogeny and ionic interactions.

The inspection of several muscular parvalbumins from different species by two NMR methods (113Cd resonance and 1H relaxation measurements) allows two classes of parvalbumins to be distinguished according to their ion-binding properties. This result is in agreement with the phylogenetic classification of parvalbumins in two series, alpha and beta, which was established on the basis of the primary structures of these proteins. All parvalbumins are characterized by the presence of two primary cationic sites CD and EF, with structural features closely related to those already known on the basis of X-ray crystallographic studies of the beta parvalbumin pI 4.25 from carp muscle. However, parvalbumins of the beta series are characterized by a secondary cation (Ca2+, Mg2+ and other cations) binding site which is absent (or at least inaccessible) in parvalbumins of the alpha series. The major component from thornback ray (pI 4.45) behaves as an alpha parvalbumin as shown by the present NMR studies, although its primary structure suggests a closer similarity with the parvalbumins of the beta series.

Animals↗
PubMed1979

NMR studies of primary and secondary sites of parvalbumins using the two paramagnetic probes Gd (III) and Mn (II).

The binding of cations by parvalbumins was studied by the proton relaxation enhancement (PRE) method using the paramagnetic probes Gd(III) and Mn(II). Gd(III) appears as a specific probe of the primary sites CD and EF with the following binding parameters: n = 2, KdGd = 0.5 x 10(-11) M and epsilon b = 2.3. The low value of epsilon b is the result of a nearly complete dehydration of the protein bound ions. Competition experiments between Gd(III) and various diamagnetic cations show the following order of affinity for the EF and CD sites: Mg2+ less than Zn2+ less than Sr2+ less than Ca2+ less than Cd2+ less than La3+ less than or equal to Gd3+. Mn 2+ is a specific probe of a secondary site with the following binding parameters: n = 1, KdMn = 0.6 x 10(-3) M and epsilon b = 17. The high value of epsilon b suggests that the protein bound Mn(II) has retained most of its hydration shell. Competition experiments between (Mn(II) and different cations show similar affinities for this site: Ca2+ less than or equal to Mg2+ less than or equal to Cd2+ less than or equal to Mn2+. This secondary site is located near the EF primary site.

Animals↗