In vitro leishmanicidal activity of benzophenanthridine alkaloids from Bocconia pearcei and related compounds.
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 (IC(50) value: 0.014 microg/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 C(7)-C(8) position was found to enhance the activity. On the other hand, the bulkiness at the C(2)-C(3) position on the D-ring, a carbonyl group at C-6, substitution at C-6 and cleavage or saturation of the C(5)-C(6) bond reduced activity. A methyl group on nitrogen of the C-ring was thought to be necessary for significant activity.
Fuchino
Hiroyuki
H
Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, 1-2 Hachimandai, Tsukuba, Ibaraki, Japan. fuchino@nibio.go.jp
Kawano
Marii
M
Mori-Yasumoto
Kanami
K
Sekita
Setsuko
S
Satake
Motoyoshi
M
Ishikawa
Tsutomu
T
Kiuchi
Fumiyuki
F
Kawahara
Nobuo
N
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D015394:Molecular Structure; D028101:Papaveraceae / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism
D000470:Alkaloids; D000981:Antiprotozoal Agents; D053119:Benzophenanthridines; D010936:Plant Extracts