title: The in vitro antitumour activity of novel, mitochondrial-interactive, gold-based lipophilic cations.
abstract: In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)(2)]Cl and [B] [Au(d4pype)(2)]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH(2))(dpmaaSnMe(2))]Cl and [D] [Au(dpmaaSnMe(2))(2)]Cl as antimitochondrial agents. The results of this study indicate that [C] and [D] have intermediate partition coefficients and exhibited a selective uptake by cells. They exhibited a higher selectivity for the various cell lines than [A] but were more cytotoxic than [B]. There is a significant correlation between the cytotoxic potential of [A], [B], [C], and [D] and their octanol/water partition coefficients in both MCF-7 (breast cancer) and MCF-12A (nonmalignant breast) cells, whereas their cytotoxic potential and ability to induce the release of cytochrome c correlated only in the case of the MCF-12A cells. Complexes [C] and [D] are promising new chemotherapeutic drugs. These compounds target the mitochondrial membranes of certain cancer cells exploiting the differences between the mitochondrial membrane potential of these cells and normal cells. Although the concentrations of these compounds necessary to eradicate cancer cells are very high, the results provide a basis for the synthesis of a new family of compounds with intermediate partition coefficients compared to [A] and [B] but with increased activity against cancer cells.
authors.affiliation: Department of Pharmacology, University of Pretoria, P.O. Box 2034, Pretoria 0001, South Africa.
authors.forename: Sherika
authors.initials: S
authors.lastname: Mahepal
authors.forename: Richard
authors.initials: R
authors.lastname: Bowen
authors.forename: Messai Adenew
authors.initials: MA
authors.lastname: Mamo
authors.forename: Marcus
authors.initials: M
authors.lastname: Layh
authors.forename: Constance Elizabeth
authors.initials: CE
authors.lastname: Jansen van Rensburg