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Synthetic ?-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 ?-hydroxytropolone-containing natural products ?-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 ?-hydroxytropolones synthesized through a convenient oxidopyrylium cycloaddition/ring-opening sequence have been tested in in vitro and cell-based assays, and have been analyzed using computational support. These studies reveal new synthetic ?-hydroxytropolones that, unlike the natural product leads they are derived from, demonstrate protective antiviral activity in cellular assays.

SUBMITTER: Murelli RP

PROVIDER: S-EPMC5234084 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Synthetic α-Hydroxytropolones as Inhibitors of HIV Reverse Transcriptase Ribonuclease H Activity.

Murelli Ryan P RP D'Erasmo Michael P MP Hirsch Danielle R DR Meck Christine C Masaoka Takashi T Wilson Jennifer A JA Zhang Baofeng B Pal Rajat K RK Gallicchio Emilio E Beutler John A JA Le Grice Stuart F J SF

MedChemComm 20160707 9

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 convenie ...[more]

PMID: 28093576

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