Antiplasmodial and Cytotoxic Activity of Natural Bisbenzylisoquinoline Alkaloids

Abstract

As part of an ongoing collaborative effort to discover new antimalarial agents from natural sources, we have tested 53 bisbenzylisoquinoline alkaloids for cytotoxicity against cultured mammalian cells and for antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant clones of Plasmodium falciparum. The isolates from Cyclea barbata, Stephania pierrei, Stephania erecta, Pachygone dasycarpa, Cyclea atjehensis, Hernandia peltata, Curare candicans, Albertisia papuana, and Berberis valdiviana exhibited a wide range of biological potencies in antiplasmodial assays, and the majority exhibited some degree of cytotoxicity against human KB cells. More than half of the compounds tested, however, showed selective antiplasmodial activity, with >100-fold greater toxicity toward one or both of the P. falciparum clones, relative to cultured mammalian cells. The most selective alkaloids were (-)-cycleanine (40), (+)-cycleatjehine (50), (+)-cycleatjehenine (49), (+)-malekulatine (3), (-)-repandine (13), and (+)-temuconine (2). As a result of these studies, relationships between the structures, the stereochemistry, and the substitution patterns of these alkaloids and their in vitro antiplasmodial and cytotoxic activities are beginning to emerge.

Antiplasmodial activity of aqueous extract ofBerberis aristataroots againstPlasmodium berghei-infected BALB/c mice

“…Berbamine (3), another alkaloid of the plant roots, exerts antimalarial activity against chloroquine-sensitive and -resistant strains of P. falciparum in vitro with the IC 50 values of 603 and 359 nM, respectively (Ye et al, 1993). A further study by Angerhofer et al (1999) suggested that 3 shows in vitro activity with an IC 50 value of 313 nM.…”

5-Hydroxytryptamine1Areceptor binding activity of bisbenzyltetrahydroisoquinoline alkaloids fromPopowia odoardi

“…natural products. They are reported to have a variety of biological activities, including antimalarial (Frappier et al, 1996), cytotoxic (Angerhofer et al, 1999), anti-HIV (Kashiwada et al, 2005), antitumor , dopamine inhibitory (Cortes et al, 1992;Protais et al, 1995), antihypertensive (Qian, 2002), antibacterial (Lohombo-Ekomba et al, 2004), and smooth muscle relaxant activity (Zafra-Polo et al, 1993). However, 5-HT 1A receptor binding activity by bisbenzylisoquinoline alkaloids has not been reported.…”

Antiplasmodial Chalcones Inhibit Sorbitol-Induced Hemolysis of Plasmodium falciparum -Infected Erythrocytes

“…The drug-sensitive cell line KB3-1 has intermediate sensitivity to cytotoxic agents and is recommended for use in the evaluation of the selectivities of antiplasmodial drugs (2). IC 50 for inhibition of hypoxanthine uptake were reported previously (18,19).…”