| Autor: |
Choroba K; Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland., Zowiślok B; Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland., Kula S; Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland., Machura B; Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland., Maroń AM; Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland., Erfurt K; Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland., Marques C; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.; Departamento de Ciências da Vida, NOVA School of Science and Technology, UCIBIO, Campus de Caparica, 2829-516 Caparica, Portugal., Cordeiro S; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.; Departamento de Ciências da Vida, NOVA School of Science and Technology, UCIBIO, Campus de Caparica, 2829-516 Caparica, Portugal., Baptista PV; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.; Departamento de Ciências da Vida, NOVA School of Science and Technology, UCIBIO, Campus de Caparica, 2829-516 Caparica, Portugal., Fernandes AR; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.; Departamento de Ciências da Vida, NOVA School of Science and Technology, UCIBIO, Campus de Caparica, 2829-516 Caparica, Portugal. |
| Abstrakt: |
Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl 2 (L n )]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes ( Cu1a and Cu1b ) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA). |
