Isolation of anti-HIV-1 lignans from Larrea tridentata by counter-current chromatography.
Several lignans, mostly new, were isolated from Larrea tridentata by assay-guided counter-current chromatography (CCC). Using the secreted alkaline phosphatase bioassay of HIV Tat transactivation and the two-phase hexane-ethyl acetate-methanol-water solvent system, two major components (Gr and Lo) were identified as anti-HIV active principles. The chemical structures of the constituents of Gr (G1-G4) and Lo (L1-L4) were determined by GC-MS and NMR. After optimization of isolation conditions, a large-scale isolation with the chloroform-methanol-water system yielded five constituents (FB1-FB5). The most predominant anti-HIV compound FB2 (denoted Malachi 4:5-6 or mal.4), which occurs in 0.23% yield, was separated from its FB1 isomer (0.13% yield). Compound FB4 and two tricyclic lignans (FB3 and FB5) were also isolated in a substantial amount for further testing of their anti-HIV activities. These compounds may represent a new class of anti-HIV agents with important clinical relevance.
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Department of Biology, Johns Hopkins University, Baltimore, MD 21218-2685, USA.
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D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology; D002855:Chromatography, Thin Layer / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D015696:Gene Products, tat / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects*; D017705:Lignans / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010865:Pilot Projects; D010946:Plants, Medicinal / Q000737:chemistry*; D015533:Transcriptional Activation / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015696:Gene Products, tat; D017705:Lignans; D054322:tat Gene Products, Human Immunodeficiency Virus