Issue 12, 2022

Enhancement of cancer-cell-selective cytotoxicity by a dicopper complex with a phenanthrene amide-tether ligand conjugate via mitochondrial apoptosis

Abstract

Dicopper complexes [Cu2(μ-OH)(Ln)](ClO4)2 [n = 1 (1) and 2 (2)] with a novel phenanthrene amide-tether ligand conjugate (HL1) and the original p-cresol-2,6-bis(amidecyclen) (HL2) were synthesized. A phenanthrene unit of 1 enhances the DNA-binding by 9-fold, enabling 1 to convert supercoiled plasmid DNA with H2O2 to a linear one in a 9.3-fold higher yield than 2. 1 reacts with H2O2 to form the μ-1,1-hydroperoxodicopper(II) complex 3 as the active species. The IC50 values of 1 against cancer cells of the lung and pancreas are 23.8 and 18.4 μM, respectively, 12-fold more toxic than the 284 and 241 μM of 2. Confocal microscopy, fluorescence-activated cell sorting, and caspase activity assays using HeLa cells revealed that 1 induces mitochondrial apoptosis. A DNA-targeting phenanthrene unit of 1 enhances the cancer-cell-selective toxicity via mitochondrial apoptosis.

Graphical abstract: Enhancement of cancer-cell-selective cytotoxicity by a dicopper complex with a phenanthrene amide-tether ligand conjugate via mitochondrial apoptosis

Supplementary files

Article information

Article type
Paper
Submitted
26 Aug 2021
Accepted
31 Jan 2022
First published
01 Feb 2022

Dalton Trans., 2022,51, 4720-4727

Enhancement of cancer-cell-selective cytotoxicity by a dicopper complex with a phenanthrene amide-tether ligand conjugate via mitochondrial apoptosis

M. Hata, I. Saito, Y. Kadoya, Y. Tanaka, Y. Hitomi and M. Kodera, Dalton Trans., 2022, 51, 4720 DOI: 10.1039/D1DT02868E

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