Antiplasmodial and Cytotoxic Activity of Natural Bisbenzylisoquinoline Alkaloids

• Published in: Journal of natural products (Washington, D.C.) Vol. 62; no. 1; pp. 59 - 66
• Main Authors: Angerhofer, Cindy K, Guinaudeau, Hélène, Wongpanich, Varima, Pezzuto, John M, Cordell, Geoffrey A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.01.1999; Glendale, AZ American Society of Pharmacognosy
• Subjects: AGENTES ANTINEOPLASTICOS; ALBERTISIA PAPUANA; ALCALOIDE QUINOLIQUE; ALCALOIDES DE LA QUINOLINA; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; ANTIMALARIALS; Antimalarials - chemistry; Antimalarials - pharmacology; ANTINEOPLASTIC AGENTS; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; ANTIPROTOZOAIRE; ANTIPROTOZOAL AGENTS; BERBERIS; BERBERIS VALDIVIANA; Biological and medical sciences; CELL CULTURE; CELL LINES; CHEMICAL COMPOSITION; CHEMICAL STRUCTURE; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; CULTIVO DE CELULAS; CULTURE DE CELLULE; CURARE CANDICANS; CYCLEA; CYCLEA BARBATA; CYTOTOXIC COMPOUNDS; DRUG PLANTS; Drug Screening Assays, Antitumor; ESPECTROMETRIA; ESTRUCTURA QUIMICA; General pharmacology; GENERO HUMANO; GENRE HUMAIN; HERNANDIA; HERNANDIA PELTATA; HERNANDIACEAE; Humans; KB CELL LINES; MANKIND; Medical sciences; MEDICAMENT CYTOSTATIQUE; MEDICAMENTOS CONTRA PROTOZOARIOS; MEDICINAL PROPERTIES; MENISPERMACEAE; Molecular Structure; PACHYGONE; PACHYGONE DASYCARPA; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; PLANTAS MEDICINALES; PLANTE MEDICINALE; PLASMODIUM FALCIPARUM; Plasmodium falciparum - drug effects; PROPIEDADES MEDICINALES; PROPRIETE PHARMACOLOGIQUE; QUINOLINE ALKALOIDS; SPECTRAL ANALYSIS; SPECTROMETRIE; SPECTROMETRY; STEPHANIA; STEPHANIA ERECTA; STEPHANIA PIERREI; STRUCTURE CHIMIQUE; Structure-Activity Relationship; SUBSTANCE TOXIQUE; SUSTANCIAS TOXICAS; TOXIC SUBSTANCES; Tumor Cells, Cultured; Antineoplastic agent; Antimalarial; Nitrogen heterocycle; Chloroquine; Cytotoxicity; Menispermaceae; Medicinal plant; Antiprotozoal agent; Plasmodium falciparum; Alkaloid; Structure activity relation; Dicotyledones; Angiospermae; Parasiticid; Bicyclic compound; Aromatic compound; Hernandiaceae; Berberidaceae; Tumor cell; Oxygen nitrogen heterocycle; Human; Protozoa; Apicomplexa; Isoquinoline derivatives; Pharmacognosy; Polycyclic compound; In vitro; Resistance; Cell line; KB cell line; Plant origin; Phenols; Spermatophyta
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np980144f

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.