Antimalarial, cytotoxic, and antifungal alkaloids from Duguetia hadrantha.
Bioassay-guided isolation of Duguetia hadrantha yielded two new 4,5-dioxo-1-azaaporphinoids, hadranthine A (1) and hadranthine B (2), together with the known alkaloids imbiline-1 (3), sampangine (4), and 3-methoxysampangine (5), whose structures were determined primarily from 2D-NMR 1H-13C HMBC, and 1H-15N HMBC experiments. This is the first report of the co-occurrence of the copyrine alkaloids 4 and 5, as well as the first report of either copyrine or imbiline type alkaloids from a Duguetia species. Compounds 1, 4, and 5 demonstrated in vitro antimalarial activity against Plasmodium falciparum (W-2 clone), while 2 was inactive. Instead, 2 showed in vitro cytotoxicity to selected human cancer cell lines (IC50 = 3-6 microg/mL against SK-MEL, KB, BT-549, and SK-OV-3), and 4 was also cytotoxic to human malignant melanoma (IC50 = 0.37 microg/mL). Sampangine (4) also inhibited cell aggregation with a MIC value of <0.15 microg/mL, while 3-methoxysampangine (5) was only weakly active.
Muhammad
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National Center for Natural Products Research and Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA. milias@olemiss.edu
Dunbar
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Takamatsu
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Walker
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Clark
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D000470:Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D000962:Antimalarials / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D001938:Brazil; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010239:Paraguay; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000935:Antifungal Agents; D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts