alexa Abstract | Antimalarial Activity of Various Bisbenzylisoquinoline and AporphineBenzylisoquinoline Alkaloids and their Structure-Activity Relationships against Chloroquine Sensitive and Resistant Plasmodium falciparum Malaria in vitro
ISSN: 2470-6965

Malaria Control & Elimination
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The antimalarial activity of some bisbenzylisoquinoline (BBIQ) alkaloids were studied using in vitro culture of both chloroquine (CQ)-sensitive and chloroquine-resistant strains of Plasmodium falciparum. The combination of chloroquine and tetrandrine gave a 44 fold potentiation of malarial killing. Fangchinoline, hernandezine, pycnamine, berbamine and isotetrandrine had similar antimalarial activity as tetrandrine against the sensitive strain of P. falciparum malaria. Hernandezine, isotetrandrine, berbamine, fangchinoline and methoxyadiantifoline had similar antimalarial activity as tetrandrine against a strain of chloroquine-resistant falciparum malaria. Based on structure/ activity analysis, we concluded that the stereochemistry of C-1ʹ (S ring) of the BBIQ structure played an important role in selective action against resistant malaria. The stereochemistry of C-1 (left ring) and a substituent of C-12 appeared to have little influence on the selectivity. The point of attachment of the ether bridges to the rings also exerts an important influence on selective antimalarial activity. Tetrandrine (TT) penetrates both the erythrocyte and parasite membranes and inhibits the synthesis and activity of the (MDR) pump and likely the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) since it inhibits the calcium channel. These observations likely account for the fact TT potentiates the activity of chloroquine more than 40 fold against chloroquine resistant falciparum malaria.

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Author(s): Zuguang Ye and Knox Van Dyke


Chloroquine sensitive and resistant falciparum malaria, Bisbenzylisoquinolines, Structure-activity, Tetrandrine, MDR: multiple drug resistance, Pfcrt: Plasmodium falciparum resistance transporter, Antimalarial,Malaria fever,Plasmodium malariae

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