title: Photophysical, photochemical, and tumor-selectivity properties of bromine derivatives of rhodamine-123.
abstract: The conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemotherapy and photochemotherapy of neoplastic diseases rests on the observation that enhanced mitochondrial membrane potential is a common tumor cell phenotype. The potential of this strategy is highlighted by the fact that the toxic effects associated with a number of cationic dyes known to localize in energized cell mitochondria are much more pronounced in tumor cells than in normal cells. Here we evaluate the phototoxic properties of four bromine derivatives of rhodamine-123 toward human uterine sarcoma (MES-SA) and green monkey kidney (CV-1) cells and compare the degrees of tumor cell selectivity associated with these dyes with those associated with two model mitochondrial triarylmethanes (crystal violet and ethyl violet). Selective phototoxicity toward tumor cells was found to be highly dependent upon the lipophilic/hydrophilic character of the cationic photosensitizer. Our experimental data have indicated that the probability of success of mitochondrial targeting in (photo)chemotherapy of neoplastic diseases is higher when the octan-1-ol/water partition coefficient of the drug candidate falls within approximately two orders of magnitude from that of the prototypical mitochondria-specific dye rhodamine-123.
authors.affiliation: University of Wisconsin, Department of Chemistry and Biochemistry, Milwaukee 53211, USA.
authors.forename: Silvia H D
authors.initials: SH
authors.lastname: Lacerda
authors.forename: Bindu
authors.initials: B
authors.lastname: Abraham
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Stringfellow
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Indig
mesh_terms: D000818:Animals; D001966:Bromine / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000627:therapeutic use; D005840:Gentian Violet / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008027:Light; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods; D020112:Rhodamine 123 / Q000031:analogs & derivatives / Q000737:chemistry* / Q000627:therapeutic use*; D012394:Rosaniline Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005456:Fluorescent Dyes; D012394:Rosaniline Dyes; D020112:Rhodamine 123; C034887:ethyl violet; D005840:Gentian Violet; D001966:Bromine