title: Synthetic α-Hydroxytropolones as Inhibitors of HIV Reverse Transcriptase Ribonuclease H Activity.
abstract: HIV Reverse Transcriptase-associated ribonuclease H activity is a promising enzymatic target for drug development that has not been successfully targeted in the clinic. While the α-hydroxytropolone-containing natural products β-thujaplicinol and manicol have emerged as some of the most potent leads described to date, structure-function studies have been limited to the natural products and semi-synthetic derivatives of manicol. Thus, a library of α-hydroxytropolones synthesized through a convenient oxidopyrylium cycloaddition/ring-opening sequence have been tested inin vitroand cell-based assays, and have been analyzed using computational support. These studies reveal new synthetic α-hydroxytropolones that, unlike the natural product leads they are derived from, demonstrate protective antiviral activity in cellular assays.
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Murelli
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: D'Erasmo
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Hirsch
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Meck
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Masaoka
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wilson
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Biochemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Rajat K
authors.initials: RK
authors.lastname: Pal
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA; PhD Program in Biochemistry, The Graduate Center of The City University of New York, New York, NY, USA.
authors.forename: Emilio
authors.initials: E
authors.lastname: Gallicchio
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
authors.forename: Stuart F J
authors.initials: SF
authors.lastname: Le Grice