Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Cinchona bark contains alkaloids like quinine, quinidine, cinchonine and cinchonidine. These agents are effective antimalarial drugs and have been used clinically in malaria caused by Plasmodium falciparum. Previous studies show that quinine and quinidine exert effects on cardiovascular system. This study was conducted to examine the effect of cinchonine on human platelet aggregation. The results show that cinchonine inhibited platelet aggregation mediated by platelet agonists, epinephrine (200 microM), ADP (4.3 microM), platelet activating factor (PAF; 800 nM) and collagen (638 nM) but had no effect on arachidonic acid (AA; 0.75 mM). Cinchonine was most effective in inhibiting aggregation induced by platelet activating factor and epinephrine with IC50 values of 125 and 180 microM respectively, however, higher concentrations of cinchonine were required to inhibit aggregation mediated by ADP or collagen (IC50; 300 microM). Pretreatment of platelets with cinchonine inhibited aggregation caused by Ca2+ ionophore, A-23187 (6 microM), in a dose-dependent manner (IC50; 300 microM) indicating an inhibitory effect on Ca2+-signaling cascade. This was supported by measuring [Ca2+]i in platelets loaded with Fura-2AM where cinchonine inhibited the rise in cytosolic Ca2+ mediated by A-23187 (6 microM) or collagen (638 nM). Results show that cinchonine (20 microM) also inhibited aggregation when platelets were pretreated with protein kinase C (PKC) activator, phorbol myristate acetate (PMA; 0.1 microM) in combination with low doses of platelet activating factor (80 nM). Cinchonine, however, had no effect on AA-induced platelet aggregation and thromboxane A2 (TXA2) synthesis in platelets. These results suggest that antiplatelet effects of cinchonine are mediated mainly through inhibition of Ca2+-influx and protein kinase C pathways in platelets.
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PMID:The inhibitory effect of cinchonine on human platelet aggregation due to blockade of calcium influx. 977 5

Cinchonine (Cin) is the primary drug of choice in the treatment of malaria, but its poor solubility has restricted its use via the oral route. Cyclodextrins (CDs) form inclusion complexes with cinchonine to form soluble complexes. This interaction was investigated by solubility studies, electrospray ionization mass spectrometry (ESI-MS), and molecular modeling. ESI-MS evaluated successfully the nature of the solution-phase inclusion complexes. The experimental results showed that not only 1:1, but also stable 2:1 inclusion complexes can be formed between CDs and Cin. Multi-component complexes of beta-CD-Cin-beta-CD (1:1:1), gamma-CD-Cin-gamma-CD (1:1:1), and beta-CD-Cin-gamma-CD (1:1:1) were found in equimolar beta- and gamma-CD mixtures with Cin. The formation of 2:1 and multi-component 1:1:1 non-covalent CD-Cin complexes indicates that beta- and gamma-CD are able to form sandwich-type inclusion complexes with Cin in high concentrations. The phase-solubility diagram showed non-linear type A(p) profile, indicating that more than one cyclodextrin molecule is involved in the complexation of one guest molecule. Molecular modeling calculations have been carried out to rationalize the experimental findings and predict the lowest energy molecular structure of inclusion complex.
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PMID:Evidence for the 2:1 molecular recognition and inclusion behaviour between beta- and gamma-cyclodextrins and cinchonine. 1521 Mar 37