Anticancer and Antimicrobial Metallopharmaceutical Agents Based on Palladium, Gold, and Silver N-Heterocyclic Carbene Complexes

Abstract

Complete synthetic, structural, and biomedical studies of two Pd complexes as well as Au and Ag complexes of 1-benzyl-3-tert-butylimidazol-2-ylidene are reported. Specifically, trans-[1-benzyl-3-tert-butylimidazol-2-ylidene]Pd(pyridine)Cl2 (1a) was synthesized from the reaction of 1-benzyl-3-tert-butylimidazolium chloride (1) with PdCl2 in the presence of K2CO3 as a base. The other palladium complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]2PdCl2 (1b), and a gold complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AuCl (1c), were synthesized by following a transmetallation route from the silver complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AgCl (1d), by treatment with (COD)PdCl2 and (SMe2)AuCl, respectively. The silver complex 1d in turn was synthesized by the reaction of 1 with Ag2O. The molecular structures of 1a-d have been determined by X-ray diffraction studies. Biomedical studies revealed that, while the palladium complexes 1a and 1b displayed potent anticancer activity, the gold (1c) and silver (1d) complexes exhibited significant antimicrobial properties. Specifically, 1b showed strong antiproliferative activity against three types of human tumor cells, namely, cervical cancer (HeLa), breast cancer (MCF-7), and colon adenocarcinoma (HCT 116), in culture. The antiproliferative activity of 1b was found to be considerably stronger than that of cisplatin. The 1b complex inhibited tumor cell proliferation by arresting the cell cycle progression at the G2 phase, preventing the mitotic entry of the cell. We present evidence suggesting that the treated cells underwent programmed cell death through a p53-dependent pathway. Though both the gold (1c) and silver (1d) complexes showed antimicrobial activity toward Bacillus subtilis, 1c was found to be ca. 2 times more potent than 1d.

Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

“…Different activities were also previously found for equivalent Ag and Au complexes with P-donor [28], S-donor [13] or N-donor ligands [47]. As an interesting example in the latter case, it was shown [47] that [1-benzyl-3-tert-butylimidazol-2-ylidene]AuCl has significant activity against B. subtilis and that this activity is higher than that of the equivalent silver complex.…”

Synthesis and comparative study on the antimicrobial activity of hybrid materials based on silver nanoparticles (AgNps) stabilized by polyvinylpyrrolidone (PVP)

“…Among them, silver nanoparticles (AgNps) are extensively studied in the recent years because of their possible usage as a strong bactericidal material with an application in biomedical field. Their pronounced antibacterial activity can be attributed to the well-developed surface and large surface area to volume ratio providing better contact with the microorganisms [3] and to the strong cytotoxicity to bacterial cells as a result of their interaction with the functional groups on the bacterial cell surface [4][5][6].…”

“…The aim of this study was to synthesize AgNps/PVP by thermal reduction of silver ions without using any reducing agent or by chemical reduction using NaBH 4 as a reducing agent and to determine the presence of antimicrobial activity of AgNps/PVP against different groups of bacteria, spores of bacteria, yeasts, and molds. There are studies in the literature concerning the antibacterial activity of AgNps stabilized by PVP against Escherichia coli and Staphylococcus aureus [14,18].…”

SYNTHESIS AND CHARACTERIZATION OF BIOLOGICALLY IMPORTANT NOVEL QUERCETIN OXIME DERIVATIVES OF Pd (II) COMPLEXES

“…[6] The redox properties of the Quercetin derivatives has been found to block cell cycle progression in a variety of malignant cell lines including those derived from the prostrate, The phytochemicals, when administered to rats, rutin has also beenfound to display chemo preventive properties, acting as an agent blocking carcinogenesis induced by heterocyclic amines. [8][9][10][11][12][13][14][15][16] …”