8 research outputs found
Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae)
BACKGROUND: Malaria, trypanosomiasis and leishmaniasis have an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. Currently, there is inadequate armory of drugs for the treatment of malaria, trypanosomiasis and leishmaniasis. This underscores the continuing need for the discovery and development of new anti-protozoal drugs. Consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe anti-plasmodial, anti-trypanosomal and anti-leishmanial drugs. METHODS: Bioassay-guided chromatographic fractionation was employed for the isolation and purification of antiprotozoal alkaloids. RESULTS: The methanol extract from the leaves of Annickia kummeriae from Tanzania exhibited a strong anti-plasmodial activity against the multi-drug resistant Plasmodium falciparum K1 strain (IC50 0.12 +/- 0.01 mug/ml, selectivity index (SI) of 250, moderate activity against Trypanosoma brucei rhodesiense STIB 900 strain (IC50 2.50 +/- 0.19 mug/ml, SI 12) and mild activity against Leishmania donovani axenic MHOM-ET-67/82 strain (IC50 9.25 +/- 0.54 mug/ml, SI 3.2). Bioassay-guided chromatographic fractionation led to the isolation of four pure alkaloids, lysicamine (1), trivalvone (2), palmatine (3), jatrorrhizine (4) and two sets of mixtures of jatrorrhizine (4) with columbamine (5) and palmatine (3) with (-)-tetrahydropalmatine (6). The alkaloids showed low cytotoxicity activity (CC50 30 - <90 mug/ml), strong to moderate anti-plasmodial activity (IC50 0.08 +/-
Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts
Palmatine, a protoberberine alkaloid, inhibits both Ca2+- and cAMP-activated Cl− secretion in isolated rat distal colon
Spectroscopic and Calorimetric Studies on the Binding of Alkaloids Berberine, Palmatine and Coralyne to Double Stranded RNA Polynucleotides
The interaction of two natural protoberberine plant alkaloids berberine and palmatine and a synthetic derivative
coralyne to three double stranded ribonucleic acids, poly(A). poly(U), poly(I).poly(C) and poly(C).poly(G)
was studied using various biophysical techniques. Absorbance and fluorescence studies showed that the alkaloids
bound cooperatively to these RNAs with the binding affinities of the order 104 M-1. Circular dichroic results
suggested that the conformation of poly(A). poly(U) was perturbed by all the three alkaloids, that of
poly(I).poly(C) by coralyne only and that of poly(C).poly(G) by none. Fluorescence quenching studies gave
evidence for partial intercalation of berberine and palmatine and complete intercalation of coralyne to these
RNA duplexes. Isothermal titration calorimetric studies revealed that the binding was characterized by negative
enthalpy and positive entropy changes and the affinity constants derived were in agreement with the overall
binding affinity from spectral data. The binding of all the three alkaloids considerably stabilized the melting
of poly(A). poly(U) and poly(I).poly(C) and the binding data evaluated from the melting data were in agreement
with that obtained from other techniques. The overall binding affinity of the alkaloids to these double stranded
RNAs varied in the order, berberine ) palmatine < coralyne. The temperature dependence of the enthalpy
changes afforded large negative values of heat capacity changes for the binding of palmatine and coralyne to
poly(A).poly(U) and of coralyne to poly(I).poly(C), suggesting substantial hydrophobic contribution in the
binding process. Further, enthalpy-entropy compensation was also seen in almost all the systems that showed
binding. These results further advance our understanding on the binding of small molecules that are specific
binders to double stranded RNA sequences
Recalcitrant organic residue compositions and the resource recovery from a food waste treatment facility
Biophysical Studies on the Effect of the 13 Position Substitution of the Anticancer Alkaloid Berberine on Its DNA Binding
The structural effects and thermodynamics of
the DNA binding of six berberine analogues with alkyl chains
of varying length and a terminal phenyl group at the C-13
position were investigated. All the analogues bound DNA
noncooperatively in contrast to the cooperative binding of
berberine. The binding affinity was higher and the effect of the
chain length was only up to (CH2)3, after which the binding
affinity decreased slightly. Intercalative binding with strong
stabilization of the DNA helix was revealed. Binding resulted in
the weakening of the base stacking with moderate conformational changes within the B-form. The binding was entropy driven in
each case, the entropy contribution to the free energy increasing with the chain length up to the threshold (CH2)3. The
complexation was dominated by nonpolyelectrolytic forces in each case; polyelectrolytic forces contributed only a quarter to the
total free energy at 50 mM [Na+]. Overall, the phenylalkyl substitution at the C-13 position considerably enhanced the DNA
binding and was highest for the analogue with (CH2)3. Structural and thermodynamic data on the DNA binding aspects of the
substituted berberines are presented in comparison with berberine