About this item:

406 Views | 437 Downloads

Author Notes:

Corresponding author: Mark T. Hamann, Email: mthamann@olemiss.edu

Subjects:

Research Funding:

This work was supported in part by grants from the National Institutes of Health: NIAID (R01 AI36596) and NCRR (P20 RR021929).

The authors would like to thank Marsha Wright for conducting the anti-microbial testing, which was supported by the NIH, NIAID, Division of AIDS, Grant No. AI 27094, and the USDA Agricultural Research Service Specific Cooperative Agreement No. 58-6408-2-0009.

Anti-malaria assays were conducted by John Trott. Additional in vitro anti-HIV data were determined at the Southern Research Institute, Frederick, MD, under NIAID Contract N01-AI-25478.

This investigation was conducted in a facility constructed with support from research facilities improvement program C06 RR-14503-01 from the NIH National Center for Research Resources.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Chemistry, Medicinal
  • Pharmacology & Pharmacy
  • BIOCHEMISTRY & MOLECULAR BIOLOGY
  • CHEMISTRY, MEDICINAL
  • aaptamine
  • alkaloid
  • anti-HIV
  • cytotoxicity
  • DNA binding
  • infectious diseases
  • natural products
  • ALPHA-BLOCKING ACTIVITY
  • SPONGE AAPTOS-AAPTOS
  • ANTINEOPLASTIC AGENTS
  • ALKALOIDS
  • ISOAAPTAMINE
  • BISDEMETHYLAAPTAMINE
  • CONVERSION
  • ORGANISMS
  • DISCOVERY
  • SYSTEMS

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

Journal Title:

Chemical Biology and Drug Design

Volume:

Volume 71, Number 3

Publisher:

, Pages 205-215

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2008 The Authors.

Export to EndNote