Biological and mechanistic activities of xanthorrizol and 4-(1',5'-dimethylhex-4'-enyl)-2-methylphenol isolated from Iostephane heterophylla.
Xanthorrizol (1) and 4-(1',5'-dimethylhex-4'-enyl)-2-methylphenol (2) were identified as the principal antimicrobial components of a CH(2)Cl(2)-MeOH (1:1) extract derived from Iostephane heterophylla. Compound 2 is a new natural product, but has been synthesized. Both compounds exhibited low level activity (MICs of 16-32 microg/mL) against methicillin-resistant staphylococci and vancomycin-resistant enterococci. They were either inactive or poorly active against Gram-negative bacteria and yeast. Mechanistic studies performed in Escherichia coli imp suggested nonspecific inhibition of DNA, RNA, and protein synthesis by both of these compounds. Compound 1 was tested in an in vivo model; it did not provide protection to mice infected with Staphylococcus aureus.
Mata
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Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México D.F. 04510, México. rachel@servidor.unam.mx
Martínez
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Bye
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Morales
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Singh
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Janso
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Maiese
W M
WM
Timmermann
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B
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008800:Mexico; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
C435265:4-(1',5'-dimethylhex-4'-enyl)-2-methylphenol; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D010636:Phenols; D011506:Proteins; C120248:xanthorrhizol; D012313:RNA; D014640:Vancomycin; D004247:DNA