Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells

Bioorg Med Chem. 2003 Sep 1;11(18):4121-31. doi: 10.1016/s0968-0896(03)00453-x.

Abstract

alpha N,(omega)N-bis(ethyl) octamine SL-11160, decamine SL-11159, dodecamine SL-11226, and tetradecamine SL-11175 were chemically synthesized. We called this class of compounds 'oligoamines'. In these compounds, each -NH(2)(+) residue is separated by four CH(2) residues. trans-Unsaturation was also introduced into the center of the oligoamine chain resulting in the trans-octamine SL-11158, trans-decamine SL-11144, trans-dodecamine SL-11172 and trans-tetradecamine SL-11227. cis-Unsaturation gave the cis-octamine SL-11157 and cis-decamine SL-11150. When assayed for their growth inhibitory effect against four human prostate cancer cell lines LnCap, DU-145, DuPro, and PC-3 by a MTT assay, the ID(50) values were less than 1 microM in all four cell lines. On day 6 of treatment, 2 microM SL-11159, SL-11144 and SL-11175 killed over five logs of DuPro cells while SL-11172 killed over four logs as determined by a colony forming efficiency (CFE) assay. In addition, SL-11159, SL-11226 and SL-11227 killed four logs of PC-3 cells. PC-3 cells are generally resistant to shorter chain polyamine analogues. Such a level of cytotoxicity in any of the prostate tumor cell lines has not been observed for any other polyamine analogues tested thus far. The DU-145 cell line was too sensitive to oligoamines to perform a CFE analysis and the DuPro cell line was too sensitive to SL-11227 treatment to obtain reproducible CFE data. Interestingly, all 10 oligoamines were efficient DNA aggregators in a cell-free system and their cytotoxicities generally parallel their capacities to aggregate DNA.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Survival
  • DNA / chemistry
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Propylamines / chemical synthesis*
  • Propylamines / pharmacology
  • Prostatic Neoplasms
  • Stereoisomerism
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Antineoplastic Agents
  • Propylamines
  • DNA