Cytotoxicity of nocobactins NA-a, NA-b and their ferric complexes assessed by semiempirical molecular orbital method.

Abstract

Nocobactins NA-a (NBNAa) and NA-b (NBNAb) showed higher cytotoxic activity against human tumor cell lines (HSC-2, HSC-3, HL-60) than against normal human cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), yielding tumor specificity indices (TS) of 80.0 and 43.9, respectively. We investigated the effect of FeCl3 on these compounds, as judged by changes in their cytotoxicity and absorption spectra. Addition of an equimolar concentration of FeCl3 almost completely abrogated the cytotoxicity and changed the pattern of absorption spectra of NBNAa and NBNAb. Mass spectrometry demonstrated that ferri-nocobactin NA-a (Fe-NBNAa) contains an iron atom, and this chelating complex had two orders lower cytotoxicity than intact NBNAa. A semi-empirical molecular orbital method (CAChe), based on these experimental data, proposed the estimated structure of Fe-NBNAa. The present study suggests that NBNAa and NBNAb are promising compounds for further study of antitumor potential in vivo, although their biological activity is significantly affected by the Fe3+ concentration in both intracellular and extracellular milieus.

• Authors: Hiroshi Sakagami, Mariko Ishihara, Yasutaka Hoshino, Jun Ishikawa, Yuzuru Mikami, Toshio Fukai
• Journal: In vivo (Athens, Greece) (In Vivo) 2005 Jan-Feb Vol. 19 Issue 1 Pg. 277-82 ISSN: 0258-851X [Print] Greece
• PMID: 15796187 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carbon Isotopes
• Ferric Compounds
• Hydroxamic Acids
• Oxazoles
• nocobactin NA-a
• nocobactin NA-b
• nocobactins

Topics

• Antineoplastic Agents (chemistry, toxicity)
• Carbon Isotopes
• Cell Line
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Ferric Compounds (chemistry, metabolism)
• HL-60 Cells
• Humans
• Hydroxamic Acids (chemistry, pharmacology, toxicity)
• Mass Spectrometry
• Mouth Neoplasms (drug therapy)
• Nuclear Magnetic Resonance, Biomolecular
• Oxazoles (chemistry, pharmacology, toxicity)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Structure-Activity Relationship