Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole

Abstract

Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = NO3− (1), ClO4− (2)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, 1H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.

Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug

“…They consist of the appropriate counter ions (nitrate and perchlorate) and silver(I) ions coordinated by two miconazole ligands. Their spectroscopic properties (IR, 1 H NMR, ESI-MS), X-ray diffraction analysis and cytotoxic potential against the HepG2 human liver cancer cell line were previously determined and reported [ 50 ].…”

“…The characteristics of the 1 H NMR spectra for [Ag(MCZ) 2 NO 3 ] ( 1 ) and [Ag(MCZ) 2 ClO 4 ] ( 2 ) complexes were described in our previous work [ 50 ]. The 1 H and 13 C NMR spectra of the newly synthesized complexes and free miconazole ligand were recorded in CDCl 3 .…”

“…The IR spectra of complexes 1 and 2 were characterized in our recent work [ 50 ]. In the miconazole spectrum, a band at 3151 cm −1 is observed, which is assigned to the CN vibration of the imidazole group [ 56 ].…”

“…This band is not observed in the spectrum of the free ligand. It can be assumed that these bands are derived from the stretching vibrations of the C═N group of the imidazole nitrogen [ 50 ]. This indicates the connection of Ag(I) ions with miconazole by the nitrogen of the imidazole group.…”

“…In our previous article, we described the synthesis of two new silver(I) complexes of miconazole, [Ag(MCZ) 2 NO 3 ( 1 )] and [Ag(MCZ) 2 ClO 4 ( 2 )], and tested their cytotoxicity using Balb/c 3T3 and HepG2 cell lines [ 50 ]. The obtained results were promising and provided a broader horizon for silver(I) complexes.…”