RT Journal Article SR Electronic T1 Cytotoxicity of Nocobactins NA-a, NA-b and their Ferric Complexes Assessed by Semiempirical Molecular Orbital Method JF In Vivo JO In Vivo FD International Institute of Anticancer Research SP 277 OP 282 VO 19 IS 1 A1 HIROSHI SAKAGAMI A1 MARIKO ISHIHARA A1 YASUTAKA HOSHINO A1 JUN ISHIKAWA A1 YUZURU MIKAMI A1 TOSHIO FUKAI YR 2005 UL http://iv.iiarjournals.org/content/19/1/277.abstract AB 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. Copyright © 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved