Antimalarial (+)-trans-hexahydrodibenzopyran derivatives from Machaerium multiflorum.
Bioassay-guided fractionation of Machaerium multiflorum yielded the hitherto unreported (+)-trans-hexahydrodibenzopyrans machaeriol A (1) and machaeriol B (2), as well as the known guaiane sesquiterpene (-)-kessane. Structure elucidation was based on (1)H and (13)C NMR data, mainly 2D NMR (1)H-(1)H COSY, (1)H-(13)C HMQC, (1)H-(13)C HMBC, and (1)H-(1)H NOESY experiments. This is the first report of the hexahydrodibenzopyrans from a higher plant other than the genus Cannabis. The cannabimimetic activity was thus evaluated by radioligand binding assay for cannabinoid receptor CB1, which indicated, notably, that both 1 and 2 were inactive. In addition, the cross reactivity of 1 and 2 toward antibodies designed for urinary metabolites of cannabinoids was evaluated with the EMIT and On Line cannabinoids assays. Both compounds showed no response at 100 000 ng/mL in both assays. Machaeriol B (2) demonstrated in vitro antimalarial activity (IC(50) = 120 ng/mL) against Plasmodium falciparum W-2 clone.
Muhammad
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National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA. milias@sunset.backbone.olemiss.edu
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Dunbar
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ElSohly
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Khan
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D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000187:drug effects; D004352:Drug Resistance, Microbial; D007887:Fabaceae / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008712:Methicillin / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010568:Peru; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013752:Tetracycline / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000962:Antimalarials; D001578:Benzopyrans; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D012717:Sesquiterpenes; C440677:kessane; C440675:machaeriol A; C440676:machaeriol B; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000666:Amphotericin B; D002738:Chloroquine; D013752:Tetracycline; D008712:Methicillin