New sugar-incorporated N-heterocyclic carbene precursors and their Ag(I) and Pd(II) complexes: Synthesis, characterization, and cytotoxicity studies

Abstract

In the present work, a new series of sugar-incorporated N-heterocyclic carbene precursors namely 1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7a), 4-methyl-1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7b), 4,5-diphenyl-1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7c), and 1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]benzimidazolium bromide (8) were synthesized by the direct reaction of the N-alkylated benzimidazoles with 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl bromide. Ag(I)–NHC complexes (9a-c, 10) of the abovementioned precursors were synthesized by in-situ reaction with Ag2O in light-excluded conditions. The transmetallation reaction technique was used to synthesize Pd(II)–NHC complexes (11a-c, 12) by the reaction of [PdCl2(MeCN)2] with corresponding Ag(I)–NHC complexes. All NHC precursors and their corresponding Ag(I) and Pd(II) complexes were spectrally characterized using 1H &13C NMR, and mass spectrometry. Further, Pd(II) complexes were evaluated for their anticancer activity against eight diverse cancer cell lines, namely; Pancreatic Adenocarcinoma (Capan-1), Colorectal Carcinoma (HCT-116), Glioblastoma (LN229), Lung Carcinoma (NCI-H1975), Acute Lymphoblastic Leukemia (DND-41), Acute Myeloid Leukemia (HL-60), Chronic Myeloid Leukemia (K562), and non-Hodgkin Lymphoma (Z138). Standard antineoplastic drugs docetaxel and etoposide were included as reference compounds. Among the tested complexes, complex 11c displayed broad activity against all tested cancer types, albeit at higher concentrations when compared to the reference drugs.