"HUMAN OVARIAN-CANCER; DRUG-RESISTANCE; P-GLYCOPROTEIN"@en . "1756-5901" . . . "The effect of replacement of the N,N-chelating ligand 1,10-phenanthroline (phen) in the Ir-III pentamethylcyclopentadienyl (Cp-star) complex [(eta(5)-Cp-star)(Ir)(phen) Cl](+) (2) with the C,N-chelating ligand 7,8-benzoquinoline (bq) to give [(eta(5)-Cp-star)(Ir)(bq)Cl] (1) on the cytotoxicity of these (CpIrIII)-Ir-star complexes toward cancer cell lines was investigated. Complex 2 is inactive, similar to other (CpIrIII)-Ir-star complexes containing the N, N-chelating ligands. In contrast, a single atom change (C- for N) in the chelating N, N ligand resulted in potency in human ovarian carcinoma cisplatin-sensitive A2780 cells, and, strikingly, 1 is active in the cisplatin-resistant human breast cancer MCF-7 and A2780/cisR cells. Replacement of the N,N-chelating ligand with the C,N-chelating ligand gives rise to increased hydrophobicity, leading to higher cellular accumulation, higher DNA-bound iridium in cells and higher cytotoxicity. The pathways involved in cellular accumulation of 1 have been further explored and compared with conventional cisplatin. The results show that both energy-independent passive diffusion and energy-dependent transport play a role in accumulation of 1." . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . "The effect of replacement of the N,N-chelating ligand 1,10-phenanthroline (phen) in the Ir-III pentamethylcyclopentadienyl (Cp-star) complex [(eta(5)-Cp-star)(Ir)(phen) Cl](+) (2) with the C,N-chelating ligand 7,8-benzoquinoline (bq) to give [(eta(5)-Cp-star)(Ir)(bq)Cl] (1) on the cytotoxicity of these (CpIrIII)-Ir-star complexes toward cancer cell lines was investigated. Complex 2 is inactive, similar to other (CpIrIII)-Ir-star complexes containing the N, N-chelating ligands. In contrast, a single atom change (C- for N) in the chelating N, N ligand resulted in potency in human ovarian carcinoma cisplatin-sensitive A2780 cells, and, strikingly, 1 is active in the cisplatin-resistant human breast cancer MCF-7 and A2780/cisR cells. Replacement of the N,N-chelating ligand with the C,N-chelating ligand gives rise to increased hydrophobicity, leading to higher cellular accumulation, higher DNA-bound iridium in cells and higher cytotoxicity. The pathways involved in cellular accumulation of 1 have been further explored and compared with conventional cisplatin. The results show that both energy-independent passive diffusion and energy-dependent transport play a role in accumulation of 1."@en . "6"^^ . . "Novohradsk\u00FD, Vojt\u011Bch" . . . . "Metallomics" . . "I, P(EE2.3.20.0057), S" . "28125" . . . "3" . "6" . . . "Vojt\u00ED\u0161kov\u00E1, Marie" . "Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl anticancer complex containing a C,N-chelating ligand" . . "Liu, Z." . "Brabec, Viktor" . . "RIV/68081707:_____/14:00428115" . "Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl anticancer complex containing a C,N-chelating ligand"@en . . "Sadler, P. J." . . "RIV/68081707:_____/14:00428115!RIV15-AV0-68081707" . . "Ka\u0161p\u00E1rkov\u00E1, Jana" . . "Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl anticancer complex containing a C,N-chelating ligand" . "9"^^ . "10.1039/c3mt00341h" . . "4"^^ . "Mechanism of cellular accumulation of an iridium(III) pentamethylcyclopentadienyl anticancer complex containing a C,N-chelating ligand"@en . "[289F1CE37EEF]" . . . "000333565800030" .