Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity

Abstract

Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties.

New Copper Complexes with N,O-Donor Ligands Based on Pyrazole Moieties Supported by 3-Substituted Acetylacetone Scaffolds

“…In particular, very little attention has been paid to the study of triorganophosphane adducts of copper(I) β-diketonates of the general formula (β-diketonate)Cu(PR 3 ) n , although a rich structural diversity can also be expected there [31][32][33][34][35][36][37][38][39][40][41][42][43]. On the other hand, very few studies on the biological activity of group 11 metal complexes of β-diketones have been reported in the literature to date [44] and copper(I)-based anticancer complexes supported by β-diketonate ligands remain an unexplored research field. Recently, as part of our continuous investigation on the chemical and biological properties of coinage metal complexes [45][46][47][48][49][50][51], we reported the first study on the syntheses, characterization and biological evaluation of new Cu(I) complexes containing triorganophosphanes and the anion of several sterically hindered the β-diketone ligands [52].…”

Half-Curcuminoids Encapsulated in Alginate–Glucosamine Hydrogel Matrices as Bioactive Delivery Systems

“…For this purpose, in parallel with symmetric β-diketone derivatives, asymmetric analogs obtained by synthesis were also studied. Because of the possibilities of functionalization of the diketonic skeleton, the marginal phenyl, and the ketone or the methylene group, the resulting asymmetric compounds have important applications in the medical field, aiming at potentiating the three areas of biological activities [ 19 , 20 , 21 , 22 , 23 , 24 ]. In recent years, hybrid materials have been studied for applications in the field of biology.…”

Synthesis and cytotoxicity studies of Cu(i) and Ag(i) complexes based on sterically hindered β-diketonates with different degrees of fluorination

“…To our knowledge, with the exception of Cu(II) derivatives of curcumin, 72,73 Casiopeinas®-like compounds (Cas III) [74][75][76][77] and analogous mixed 1,10-phenanthroline and 4,4,4-trifluoro-1phenyl-1,3-butanedionate, 78 2,2-bipyridine and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedionate 79,80 or benzoylacetonate, 81 acetylacetonate 82 and 2-thenoyltrifluoroacetonate, 83 very few studies on the anticancer activity of group 11 metal complexes of β-diketones have been reported in the literature to date. 84 Copper(I)-and silver(I)-based anticancer complexes supported by β-diketonate ligands remain an unexplored research field. Therefore, as part of our continuous investigation on the chemical and biological properties of copper-and silver-containing coordination compounds, [85][86][87][88][89][90][91] we report here for the first time a study on the syntheses, characterization and biological evaluation of new Ag(I) and Cu(I) complexes containing phosphanes and the anion of the β-diketone ligands, 1,3-dimesitylpropane-1,3-dione (HL Mes ), 1,3-bis(3,5-bis(trifluoromethyl) phenyl)-3-hydroxyprop-2-en-1-one (HL CF3 ) and 1,3-diphenylpropane-1,3-dione (HL Ph ).…”