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Isoxazole‐Derived Aroylhydrazones and Their Dinuclear Copper(II) Complexes Show Antiproliferative Activity on Breast Cancer Cells with a Potentially Alternative Mechanism Of Action
Author(s) -
Rada Jesica Paola,
Forté Jéremy,
Gontard Geoffrey,
Corcé Vincent,
Salmain Michèle,
Rey Nicolás A.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000122
Subject(s) - isoxazole , chemistry , chelation , substituent , stereochemistry , cytotoxicity , pyridine , mechanism of action , ligand (biochemistry) , copper , combinatorial chemistry , in vitro , medicinal chemistry , receptor , biochemistry , organic chemistry
Abstract This paper reports the design, synthesis and cytotoxicity studies of two new isoxazole‐derived aroylhydrazone ligands and their dinuclear copper(II) complexes. Compounds were fully characterized by various spectroscopic and analytical techniques. The molecular structures of four derivatives were confirmed by X‐ray crystallography. The stability of the ligands and the complexes in aqueous medium was monitored spectroscopically. Both the ligands and the complexes were shown to interact with calf thymus DNA (ct‐DNA). Additionally, structures containing a phenol pendant arm were significantly more cytotoxic than those carrying a pendant pyridine substituent, reaching sub‐micromolar IC 50 values on the triple‐negative human breast cancer cell line MDA‐MB‐231. The metal chelation and transchelation ability of the compounds towards Fe II , Fe III and Zn II ions was explored as a possible mechanism of action of these compounds.