A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β

  • Molecules. 2020 Dec 11;25(24):5847. doi: 10.3390/molecules25245847.
Satheesh Gujarathi  1 ,  Maroof Khan Zafar  2 ,  Xingui Liu  1 ,  Robert L Eoff  2 ,  Guangrong Zheng  1  3
Affiliations
  • 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • 2. Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • 3. Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
PMID: 33322249 DOI: 10.3390/molecules25245847
Abstract

Garcinoic acid has been identified as an inhibitor of DNA Polymerase β (pol β). However, no structure-activity relationship (SAR) studies of garcinoic acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method for this natural product and its analogs. We developed an efficient semi-synthetic method for garcinoic acid and its analogs by starting from natural product δ-tocotrienol. Our preliminary SAR studies provided a valuable insight into future discovery of garcinoic acid-based pol β inhibitors.

Keywords
DNA polymerase β; garcinoic acid; semi-synthesis; structure-activity-relationship; δ-tocotrienol.
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