Synthesis and bioevaluation of N-(arylalkyl)-homospermidine conjugates

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4471-5. doi: 10.1016/j.bmcl.2007.06.009. Epub 2007 Jun 8.

Abstract

N1-(Arylalkyl)homospermidines (1c-1f) and terminally piperazine-substituted homospermidine conjugates (2a-2e) were synthesized and evaluated for cytotoxicity in mouse leukemia L1210, alpha-difluoromethylornithine (DFMO)-treated L1210, melanoma B16, spermidine (SPD)-treated B16, and HeLa cell lines. Results demonstrated that homospermidine was a more effective vector than piperazine-substituted homospermidine in ferrying diverse arenes into cells via the polyamine transporter. The leading compound, 9-anthracenemethyl-homospermidine (1a), was shown to induce apoptosis in B16 cells and IL-3 dependent FL5.12A pro-B cells. The novel conjugate 4-biphenylmethyl-homospermidine (1e) could also induce apoptosis. However, it exhibited different effect on the cell cycle of B16 cells compared to 1a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-3 / pharmacology
  • Mice
  • Molecular Structure
  • Spermidine / analogs & derivatives*
  • Spermidine / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Interleukin-3
  • Spermidine