Novel luminescent benzopyranothiophene- and BODIPY-derived aroylhydrazonic ligands and their dicopper(II) complexes: syntheses, antiproliferative activity and cellular uptake studies

Abstract

Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 3, derived from the BPT-containing ligand H3L1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed. Additionally, the stability of the ligands and complexes was monitored by UV-visible spectroscopy in DMSO and biologically relevant media. All the compounds showed moderate to high cytotoxicity towards the triple negative human breast cancer cell line MDA-MB-231. BPT derivatives were the most cytotoxic, specially H3L1, reaching an IC5O value up to the nanomolar range. Finally, fluorescence microscopy imaging studies employing mitochondria-and nucleus-staining dyes showed that the BODIPY-carrying ligand H3L2 was highly cell permeant and suggested that the compound preferentially accumulates in the mitochondria.

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

“…On the other hand, an important development in cancer research is the use of physiological metal ion complexes, which afford more biocompatibility and thus less side-effects in therapy [23]. In this sense, we have reported dicopper(II) complexes from different N-acylhydrazonic binucleating ligands with potent antiproliferative activity against a panel of cancer cell lines [24][25][26].…”

Copper(ii) complexes of a furan-containing aroylhydrazonic ligand: syntheses, structural studies, solution chemistry and interaction with HSA

“…Dinuclear copper( ii ) species have been shown to possess antiproliferative activity as well, 31–38 especially those derived from binucleating hydrazonic ligands. 24,39,40…”

“…30 Dinuclear copper(II) species have been shown to possess antiproliferative activity as well, [31][32][33][34][35][36][37][38] especially those derived from binucleating hydrazonic ligands. 24,39,40 In this context, the present work reports the syntheses of new mononuclear and dinuclear copper(II) complexes, namely [Cu(HL)Cl]•H 2 O (1) and [CuL(i-PrOH)] 2 (2), derived from 5-methylsalicylaldehyde 2-furoyl hydrazone (H 2 L, Scheme 1). Compounds were structurally and spectroscopically characterized.…”

Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action

“…Thus far, anti-malarial metal complexes are mostly mononuclear. However, despite some dicopper(II) and dizinc(II) complexes known to have anticancer property, there seems no report of their anti-malarial property [ 12 – 15 ]. Herein, the manuscript reports the synthesis and characterization of two dinuclear metal(II) complexes (Cu and Zn) with a bioactive 1,10-phenanthroline (phen) and a non-bioactive 4,4'-bipyridine (4,4’-bipy) as bridging ligand, and their anti-malarial property, with comparison to their respective mononuclear metal(II) complexes containing two phen ligands.…”