Isoxazole‐Derived Aroylhydrazones and Their Dinuclear Copper(II) Complexes Show Antiproliferative Activity on Breast Cancer Cells with a Potentially Alternative Mechanism Of Action. (19th May 2020)

• Record Type: Journal Article
• Authors: Rada, Jesica Paola; Forté, Jéremy; Gontard, Geoffrey; Corcé, Vincent; Salmain, Michèle; Rey, Nicolás A.
• Is Part Of: Chembiochem. Volume 21:Number 17(2020)
• Page Start: 2474
• Page End: 2486
• Publication Date: 2020-05-19
• Subjects: antitumor agents -- aroylhydrazonic ligands -- copper(II) complexes -- cytotoxicity -- DNA; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000122
• Languages: English
• ISSNs: 1439-4227

Abstract

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 IC50 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. Abstract : Cytotoxicity contrast : Two aroylhydrazonic ligands and their acetate/perchlorate dicopper complexes were synthesized and characterized by various spectroscopic and analytical techniques, including X‐ray diffraction. They were shown to interact with DNA and display contrasted cytotoxicity on breast cancer cells. Their biological properties were linked to their ability to undergo chelation/transmetallation with biologically relevant metal ions.