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Design, synthesis, and evaluation of phosphorescent Ir(III) complexes with anticancer activity.
Liu, Zhe; Li, JuanJuan; Ge, XingXing; Zhang, Shumiao; Xu, Zhishan; Gao, Wenyuan.
Afiliación
  • Liu Z; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China. Elect
  • Li J; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.
  • Ge X; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.
  • Zhang S; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.
  • Xu Z; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China; Depar
  • Gao W; Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.
J Inorg Biochem ; 197: 110703, 2019 08.
Article en En | MEDLINE | ID: mdl-31077890
A range of phosphorescent Ir(III) complexes containing four diverse P^P-chelating ligands of the type [Ir(ppy)2(L)][PF6], (ppy = 2­phenylpyridine) where L is 1,2­bis(diphenylphosphino)benzene (L1), 1,2­bis(diphenylphosphino)ethane (L2), 1,2­bis(diphenylphosphino)propane(L3) and 1,8­bis(diphenylphosphino)naphthalene (L4) were synthesized respectively. The iridium complexes possessed excellent antiproliferative properties, which was a substantial improvement over cisplatin, especially complex Ir1. Generally, the order of in vitro antiproliferative activity of the complexes is Ir1 > Ir2 = Ir3 > Ir4 > CDDP (Cisplatin). Two X-ray crystal structures were determined. The best complex, Ir1, was chosen to further study the mechanism of action. The self-luminescence of complex Ir1 was also successfully used to elucidate the subcellular localization. Complex Ir1 was specifically targeted to lysosomes in A549 cancer cells. This targeting caused lysosomal damage and the induction of ROS (reactive oxygen species) production in cancer cells. Flow cytometry studies confirmed that this complex induced apoptosis, especially late apoptosis. Our results suggested that changes in the mitochondrial membrane potential were responsible for apoptosis. The chemistry and biological studies showed that this class of metal complexes is worthy of further exploration to design novel anticancer drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Colorantes Fluorescentes / Iridio / Lisosomas / Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Colorantes Fluorescentes / Iridio / Lisosomas / Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos