Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

Abstract

Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

• Authors: V Pavlov, P Kong Thoo Lin, V Rodilla
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 137 Issue 1 Pg. 15-24 (Jul 31 2001) ISSN: 0009-2797 [Print] Ireland
• PMID: 11518561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polyamines
• Quinolones
• bisnaphthalimidopropylspermidine
• DNA
• Spermidine

Topics

• Breast Neoplasms
• Cell Division (drug effects)
• DNA (metabolism)
• Female
• Humans
• Microscopy, Fluorescence
• Molecular Structure
• Polyamines (chemical synthesis, chemistry, metabolism, pharmacology)
• Quinolones (chemical synthesis, chemistry, metabolism, pharmacology)
• Spectrometry, Fluorescence
• Spermidine (analogs & derivatives, chemical synthesis, chemistry, metabolism, pharmacology)
• Tumor Cells, Cultured