Plasmodium falciparum: in vitro interaction of quassin and neo-quassin with artesunate, a hemisuccinate derivative of artemisinin.
Quassia amara L. (Family Simaroubaceae) is known to have several medicinal properties including the activity against malaria. An HPLC method was employed for purification of the biologically active quassinoids; quassin (Q) and neo-quassin (NQ), further characterized by MALDI-TOF analyses. Purified Q, NQ and the crude bark extract (S1) along with artesunate (AS) were studied for their in vitro anti-plasmodial activity. The in vivo toxicity studies at intraperitoneal doses with higher concentrations of the crude bark extract (S1) in Balb/C mice ruled out the apprehension of toxicity. Interaction studies between the test compounds among themselves (Q+NQ) and individually with artesunate (AS+Q, AS+NQ), were carried out in vitro at four ratios (1:5, 1:2, 2:1 and 5:1) on chloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum. The crude bark extracts of Q. amara exhibited higher P. falciparum inhibitory activity (IC(50)=0.0025 microg/ml) as compared to that of the isolated compounds, quassin (IC(50)=0.06 microg/ml, 0.15 microM), neo-quassin (IC(50)=0.04 microg/ml, 0.1 microM) and also to the positive control, artesunate (IC(50)=0.02 microg/ml, 0.05 microM). The in vitro drug interaction study revealed the compounds, quassin and neo-quassin to be additive to each other. At lower ratios, artesunate was found to be a potential combination partner with both the compounds. It was interesting to note that none of the combinations exhibited antagonistic interactions. This phenomenon offers the opportunity for further exploration of novel therapeutic concentrations and combinations.
Mishra
Kirti
K
Institute of Life Sciences, Nalco Square, Chandrasekhar Pur, Bhubaneswar 751 023, Orissa, India. mishrak2002@yahoo.co.in
Chakraborty
Dipjyoti
D
Pal
Amita
A
Dey
Nrisingha
N
D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects*; D032271:Quassia / Q000737:chemistry; D036702:Quassins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000962:Antimalarials; D037621:Artemisinins; D010936:Plant Extracts; D036702:Quassins; D000077332:Artesunate; C539436:neoquassin; C010317:quassin