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Biomedical subjects

C Galeffi

Publications and source records attributed to C Galeffi.

At least 19 recordsLinked to original sources

In vitro and in vivo chloroquine-potentiating action of Strychnos myrtoides alkaloids against chloroquine-resistant strains of Plasmodium malaria.

Crude alkaloids of Strychnos myrtoides Gilg & Busse, empirically used as an adjuvant to chloroquine (CQ) in Malagasy herbal remedies, were practically devoid of intrinsic in vitro and in vivo antimalarial activity. However, when combined with CQ at a dose level much lower than their IC50 value, they markedly enhanced in vitro the effectiveness of the synthetic drug against a CQ-resistant strain of Plasmodium falciparum. They also enhanced in vivo CQ activity against a resistant strain of Plasmodium yoelii. By counter-current distribution (CCD) separation of the crude alkaloid extract, the two major alkaloids strychnobrasiline (1) and malagashanine (2), together with four minor alkaloids, were isolated. Strychnobrasiline and malagashanine were devoid of both intrinsic antimalarial activity and cytotoxicity effect, but exhibited significant CQ-potentiating actions. These findings could account for the above-mentioned empirical use of S. myrtoides. The present state of research on antimalarial drug from Strychnos genus is also discussed.

Alkaloids

Hypoxidaceae. Medicinal uses and the norlignan constituents.

Glycosides of uncommon aglucones, characterized by the Ph-C5-Ph skeleton, were isolated from the rhizomes of some African Hypoxis species. HPLC analysis indicated the occurrence of these compounds in other Hypoxidaceae. On the basis of structural evidence and biogenetic considerations, the aglucones of these glycosides can be considered as norlignans, derived from the union of two phenylpropanoid units in positions alpha, beta' or beta, gamma' and with the loss of the terminal carbon of a chain. Several Hypoxis species are used in traditional medicine as antiinflammatory and antitumor drugs and, recently, preparations based on lipophilic extracts of H. rooperi have been introduced into the market for the treatment of prostatic hypertrophy.

Chromatography, High Pressure Liquid

[Orphan drugs].

Diseases lacking in satisfactory therapies, named orphans (over 60% of the known), raise the problem of the availability of new drugs to be discovered and evaluated on toxicological and clinical bases. The estimated cost for the full development of a drug makes it not profitable (and therefore orphan drug) in the case of rare diseases and the typical diseases of developing countries. The USA with the Orphan Drug Act have faced the former, whereas WHO with the "Tropical Diseases Research" programme has faced the latter. Uncommon formulations and dosages of known substances and products no longer marketed as non-profitable are considered orphans drugs as well.

Centers for Disease Control and Prevention, U.S.

Effects of mansonones on lipid peroxidation, P450 monooxygenase activity, and superoxide anion generation by rat liver microsomes.

Several structurally related ortho-naphthoquinones isolated from Mansonia altissima Chev (mansonones C, E and F) (a) inhibited NADPH-dependent, iron-catalyzed microsomal lipid peroxidation; (b) prevented NADPH-dependent cytochrome P450 destruction; (c) inhibited NADPH-supported aniline 4-hydroxylase activity; (d) inhibited Fe(III)ADP reduction by NADPH-supplemented microsomes; (e) stimulated superoxide anion generation by NADPH-supplemented microsomes; and (f) stimulated ascorbate oxidation. ESR investigation of ascorbate-reduced mansonone F demonstrated semiquinone formation. Mansonone C had a greater effect than mansonones E and F on NADPH-dependent lipid peroxidation, O2- production and ascorbate oxidation, whereas mansonone E was more effective than mansonones C and F on aniline 4-hydroxylase activity. Mansonones E and F did not inhibit hydroperoxide-dependent lipid peroxidation, cytochrome P450 destruction or microsomal aniline 4-hydroxylase activity. Mansonone C inhibited to a limited degree tert-butyl hydroperoxide-dependent lipid peroxidation, this inhibition being increased by NADPH. Mansonone A, a tetrahydro orthonapthoquinone derivative, was in all respects relatively less effective than mansonones C, E and F. It is postulated that mansonones C, E and F inhibited microsomal lipid peroxidation and cytochrome P450 catalyzed reactions by diverting reducing equivalents from NADPH to dioxygen, but mansonone C (including its reduced form) may also exert direct antioxidant activity.

Animals

New trends in the separation of active principles from plants.

The extraction and separation of active principles of plant constituents is a difficult task, even for specialized chemists, when many similar substances are found in a single plant. In the case of the presence of alkaloids a separation method based on counter-current distribution with a discontinuous variation of pH can be used for the resolution of very complex mixtures. The alkaloids separated from twenty-seven medicinal plants are reported.

Alkaloids

New curare alkaloids. II. New bisbenzylisoquinoline alkaloids from Abuta grisebachii (Menispermaceae).

From Abuta grisebachii Triana & Planchon, Menispermacea used by Sanama tribe for the preparation of curare, five bisbenzylisoquinoline alkaloids have been isolated; four of them are tertiary (peinamine and three new alkaloids, 7-O-demethylpeinamine, N-methyl,7-O-demethylpeinamine and macolidine) and one is a new quaternary alkaloid called macoline. Their structures have been elucidated on the basis of chemical reactions and spectroscopic data.

Alkaloids