In Vitro Leishmanicidal Activity of Benzophenanthridine Alkaloids from Bocconia pearcei and Related Compounds

• Published in: Chemical & Pharmaceutical Bulletin Vol. 58; no. 8; pp. 1047 - 1050
• Main Authors: Fuchino, Hiroyuki, Kawano, Marii, Mori-Yasumoto, Kanami, Sekita, Setsuko, Satake, Motoyoshi, Ishikawa, Tsutomu, Kiuchi, Fumiyuki, Kawahara, Nobuo
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.08.2010; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: alkaloid; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; benzophenanthridine; Benzophenanthridines - chemistry; Benzophenanthridines - isolation & purification; Benzophenanthridines - pharmacology; Bocconia; Bocconia pearcei; Fruit - chemistry; Leishmania - drug effects; Leishmania - growth & development; leishmaniasis; Molecular Structure; Papaveraceae; Papaveraceae - chemistry; Parasitic Sensitivity Tests; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Stereoisomerism
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.58.1047

Leishmanicidal activities of benzophenanthridine alkaloids isolated from fruits of Bocconia pearcei and their derivatives were examined. Seven benzophenanthridine compounds were isolated from the methanolic extracts of B. pearcei. Among them, dihydrosanguinarine showed the most potent leishmanicidal activities (IC50 value: 0.014 μg/ml, respectively). To examine the structure–activity relationship of the benzophenanthridine skeleton, the leishmanicidal activities for 32 synthetic samples were examined. The existence of bulky groups at the C7–C8 position was found to enhance the activity. On the other hand, the bulkiness at the C2–C3 position on the D-ring, a carbonyl group at C-6, substitution at C-6 and cleavage or saturation of the C5–C6 bond reduced activity. A methyl group on nitrogen of the C-ring was thought to be necessary for significant activity.