title: Avarol restores the altered prostaglandin and leukotriene metabolism in monocytes infected with human immunodeficiency virus type 1.
abstract: Infection of monocytes with human immunodeficiency virus type 1 (HIV-1) (strain Ada-M) caused increased levels of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in vitro. These two products result from the activities of the two enzymes cyclooxygenase and 5-lipoxygenase. The addition of the sesquiterpenoid hydroquinone Avarol, an HIV inhibitor, strongly reduced the levels of LTB4 and PGE2 via inhibition of both cyclooxygenase and lipoxygenase in monocytes. The 50% inhibition concentrations (IC50) for the enzymes were determined to be 2.26 microM (cyclooxygenase) and 1.97 microM (lipoxygenase). A 50% reduction of the extent of PGE2 and LTB4 production in HIV-infected monocytes was measured at a concentration of 0.9 microM Avarol, a dose which caused an 80% anti-HIV effect in vitro (50% inhibition of virus release from infected cells: 0.3 microM). We conclude that Avarol inhibits the enzymes cyclooxygenase and lipoxygenase and suggest that, in general, inhibitors of these enzymes are promising anti-HIV compounds.
authors.affiliation: Abteilung Angewandte Molekularbiologie, Universität, Mainz, Germany.
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.forename: M E
authors.initials: ME
authors.lastname: Bégin
authors.forename: R
authors.initials: R
authors.lastname: Klöcking
authors.forename: E
authors.initials: E
authors.lastname: Matthes
authors.forename: A S
authors.initials: AS
authors.lastname: Sarma
authors.forename: M
authors.initials: M
authors.lastname: Gasić
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D007975:Leukotriene B4 / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D012717:Sesquiterpenes; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C023663:avarol