RRC ID 1126
Author Sakagami H, Ishihara M, Hoshino Y, Ishikawa J, Mikami Y, Fukai T.
Title Cytotoxicity of nocobactins NA-a, NA-b and their ferric complexes assessed by semiempirical molecular orbital method.
Journal In Vivo
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.
Volume 19(1)
Pages 277-82
Published 2005-1
PMID 15796187
MeSH Antineoplastic Agents / chemistry Antineoplastic Agents / toxicity* Carbon Isotopes Cell Line Cell Line, Tumor Drug Screening Assays, Antitumor Ferric Compounds / chemistry Ferric Compounds / metabolism* HL-60 Cells Humans Hydroxamic Acids / chemistry Hydroxamic Acids / pharmacology Hydroxamic Acids / toxicity Mass Spectrometry Mouth Neoplasms / drug therapy* Nuclear Magnetic Resonance, Biomolecular Oxazoles / chemistry* Oxazoles / pharmacology Oxazoles / toxicity* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Structure-Activity Relationship
IF 1.116
Times Cited 7
Pathogenic microorganisms IFM 10152