Antiviral and anticancer optimization studies of the DNA-binding marine natural product aaptamine

Academic Article


  • Aaptamine has potent cytotoxicity that may be explained by its ability to intercalate DNA. Aaptamine was evaluated for its ability to bind to DNA to validate DNA binding as the primary mechanism of cytotoxicity. Based on UV-vis absorbance titration data, the Kobs for aaptamine was 4.0 (±0.2) × 103 which was essentially equivalent to the known DNA intercalator N-[2-(diethylamino)ethyl]-9-aminoacridine-4-carboxamide. Semi-synthetic core modifications were performed to improve the general structural diversity of known aaptamine analogs and vary its absorption characteristics. Overall, 26 aaptamine derivatives were synthesized which consisted of a simple homologous range of mono and di-N-alkylations as well as some 9-O-sulfonylation and bis-O-isoaaptamine dimer products. Each product was evaluated for activity in a variety of whole cell and viral assays including a unique solid tumor disk diffusion assay. Details of aaptamine's DNA-binding activity and its derivatives' whole cell and viral assay results are discussed. © 2008 The Authors.
  • Digital Object Identifier (doi)

    Author List

  • Bowling JJ; Pennaka HK; Ivey K; Wahyuono S; Kelly M; Schinazi RF; Valeriote FA; Graves DE; Hamann MT
  • Start Page

  • 205
  • End Page

  • 215
  • Volume

  • 71
  • Issue

  • 3