Novel Benzyl‐ or 4‐Cyanobenzyl‐Substituted N‐Heterocyclic (Bromo)(carbene)silver(I) and (Carbene)(chloro)gold(I) Complexes: Synthesis and Preliminary Cytotoxicity Studies

Abstract

N-Heterocyclic carbene (NHC) complexes bromo(1,3-dibenzyl-1,3-dihydro-2H-imidazol-2-ylidene)silver(I) (2a), bromo[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-imidazol-2-ylidene]silver(I) (2b), and bromo[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-ylidene]silver(I) (2c) were prepared by the reaction of 1,3-dibenzyl-1H-imidazol-3-ium bromide (1a), 3-(4-cyanobenzyl)-1-methyl-1H-imidazol-3-ium bromide (1b), and 3-(4-cyanobenzyl)-1-methyl-1H-benzimidazol-3-ium bromide (1c), respectively, with silver(I) oxide. NHC Complexes chloro(1,3-dibenzyl-1,3-dihydro-2H-imidazol-2-ylidene)gold(I) (3a), chloro[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) (3b), and chloro[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-ylidene]gold(I) (3c) were prepared via transmetallation of corresponding (bromo)(NHC)silver(I) complexes with chloro(dimethylsulfido)gold(I). The complex 3a was characterized in two polymorphic forms by single-crystal X-ray diffraction showing two rotamers in the solid state. The cytotoxicities of all three bromo(NHC)silver(I) complexes and three (chloro)(NHC)gold(I) complexes were investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bormide (MTT)-based preliminary in vitro testing on the Caki-1 cell line in order to determine their IC 50 values. (Bromo)(NHC)silver(I) complexes 2a -2c and (chloro)(NHC)gold(I) complexes 3a -3c were found to have IC 50 values of 27 AE 2, 28 AE 2, 34 AE 6, 10 AE 1, 12 AE 5, and 12 AE 3 mm, respectively, on the Caki-1 cell line.

Novel symmetrically p-benzyl-substituted 4,5-diaryl-imidazole N-heterocyclic carbene-silver(I) acetate complexes – Synthesis and biological evaluation

“…As previously reported by us, novel benzyl-substituted Nheterocyclic carbene-silver [11e17] and carbeneegold complexes [18,19] exhibited good activity against the cancer cell line Caki-1 (renal) and antibacterial activity against the strains Escherichia coli and Staphylococcus aureus.…”

Adjusting the DNA Interaction and Anticancer Activity of Pt(II) N-Heterocyclic Carbene Complexes by Steric Shielding of the Trans Leaving Group

“…Melting points are uncorrected; IR spectra were recorded on an FT-IR spectrophotometer with ATR sampling unit; NMR spectra were run on 300 MHz 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 and its silver carbene complex 1 were prepared according to the literature. 17,18 All tested compounds were > 95% pure by elemental analysis or UPLC/HRMS.…”

N -Heterocyclic Carbene Metal Complexes as Bio-Organometallic Antimicrobial and Anticancer Drugs

“…In the recent past, we also reported the preliminary cytotoxicity (refers to a substance or process which results in cell damage or cell death) studies of three new benzyl-or 4-cyanobenzyl-substituted NHC-gold(I) complexes 77 and 78a-b on the human renal cancer cell line Caki-1. The NHC-gold(I) complex 77, however, gave a superior IC 50 value of 10 μm [130].…”

“…HT-29 63.8 ± 6.7 [129] 73a(Rea) HeLa 52.7 ± 5.0 [129] 73a(Rea) HepG2 71.3 ± 5.9 [129] 73a(Rea) HT-29 58.9 ± 4.3 [129] 73c(CV) HeLa 41.3 ± 10.4 [129] 73c(CV) HepG2 - [129] 73c(CV) HT-29 125.8 ± 49.7 [129] 73c(Rea) HeLa 36.2 ± 12.9 [129] 73c(Rea) HepG2 - [129] 73c(Rea) HT-29 282.5 ± 41.8 [129] 74(CV) HeLa 3.3 ± 0.9 [129] 74(CV) HepG2 4.7 ± 2.5 [129] 74(CV) HT-29 2.8 ± 1.7 [129] 74(Rea) HeLa 5.8 ± 1.9 [129] 74(Rea) HepG2 - [129] 74(Rea) HT-29 5.2 ± 3.0 [129] 75(CV) HeLa 3.4 ± 1.3 [129] 75(CV) HepG2 15.2 ± 1.7 [129] 75(CV) HT-29 10.5 ± 1.9 [129] 75(Rea) HeLa 8.3 ± 1.4 [129] 75(Rea) HepG2 20.4 ± 0.9 [129] 75(Rea) HT-29 16.9 ± 1.7 [129] 76(CV) HeLa 17.3 ± 3 [129] 76(CV) HepG2 28.1 ± 4.5 [129] 76(CV) HT-29 26.8 ± 2.1 [129] 76(Rea) HeLa 29.4 ± 1.8 [129] 76(Rea) HepG2 30.0 ± 2.6 [129] 76(Rea) HT-29 34.6 ± 1.8 [129] 77 Caki-1 10 ± 1 [130] 78a Caki-1 12 ± 5 [130] 78b Caki-1 12 ± 3 [130] 79a A2780 16.2 ± 2.1 [131] 79a A2780/R 15.6 ± 2.7 [131] 79a SKOV3 62.7 ± 7.8 [131] 79a A549 >100 [131] 79a HEK293T >100 [131] 79b A2780 26.0 ± 2.2 [131] 79b A2780/R 17.2 ± 1.7 [131] 79b SKOV3 60 ± 14 [131] 79b A549 52.8 ± 5.2 …”