From the reaction of 1-methylimidazole (1a), 4,5-dichloro-1H-imidazole (1b(I)) and 1-methylbenzimidazole (1c) with p-cyanobenzyl bromide (2a), non-symmetrically substituted N-heterocyclic carbene (NHC) [(3a-c)] precursors, 5,6-dimethyl-1H-benzimidazole (1d) and 4,5-diphenyl-1H-imidazole (1e) with p-cyanobenzyl bromide (2a) and benzyl bromide (2b), symmetrically substituted N-heterocyclic carbene (NHC) [(3d-f)] precursors were synthesised. These NHC-precursors were then reacted with silver(i) acetate to yield the NHC-silver complexes (1-methyl-3-(4-cyanobenzyl)imidazole-2-ylidene)silver(i)acetate (4a), (4,5-dichloro-1-(4-cyanobenzyl)-3-methyl)imidazole-2-ylidene)silver(i)acetate (4b), (1-methyl-3-(4-cyanobenzyl)benzimidazole-2-ylidene)silver(i)acetate (4c), (1,3-bis(4-cyanobenzyl)5,6-dimethylbenzimidazole-2-ylidene) silver(i) acetate (4d), (1,3-dibenzyl-5,6-dimethylbenzimidazole-2-ylidene) silver(i) acetate (4e) and (1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene) silver(i) acetate (4f) respectively. Three NHC-precursors 3c-e and four NHC-silver complexes 4b and 4d-f were characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial activity of the NHC-precursors and NHC-silver complexes was investigated against Gram-positive bacteria Staphylococcus aureus, and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk-diffusion method. NHC-silver complexes have shown very high antibacterial activity compared to the NHC-precursors. All six NHC-silver complexes were tested for their cytotoxicity through MTT based in vitro tests on the human renal-cancer cell line Caki-1 in order to determine their IC₅₀ values. NHC-silver complexes 4a-f were found to have IC₅₀ values of 6.2 (±1.0), 7.7 (±1.6), 1.2 (±0.6), 10.8 (±1.9), 24.2 (±1.8) and 13.6 (±1.0) μM, respectively. These values represent improved cytotoxicity against Caki-1, most notably for 4c, which is a three times more cytotoxic than cisplatin (IC₅₀ value = 3.3 μM) itself.
The design and synthesis of the new amino acid Schiff base, N-(2-hydroxy-1-naphthalidene)phenylglycine (Hhnpg) has been described along with the single crystal X-ray crystallographic studies. Copper(II), nickel(II), cobalt(II), manganese(II) and zinc(II) complexes of Hhnpg were synthesized for the first time, and were characterized on the basis of elemental analysis, conductivity measurements, spectral (i.r., 1 H-n.m.r., u.v.-vis., e.p.r.), magnetic and thermal studies. The i.r. spectral studies of all the complexes exhibit a similar feature about the ligating nature of the ligand to the metal ions and reveal that the ligand has coordinated through the carbonyl oxygen, azomethine nitrogen and deprotonated hydroxyl oxygen. The conductance data of the complexes suggest them to be nonelectrolytes. The microbial activity of the ligand and the complexes was investigated.
p‐Methoxybenzyl‐substituted and benzyl‐substituted N‐heterocyclic carbene (NHC) [(3a–c) and (6a–c)] precursors were synthesised from the reaction of 1H‐imidazole (1a), 4,5‐dichloro‐1H‐imidazole (1b), and 1H‐benzimidazole (1c) with p‐methoxybenzyl bromide (2) and benzyl bromide (5). These NHC precursors were then treated with silver(I) acetate to yield the NHC–silver complexes [1,3‐bis(4‐methoxybenzyl)imidazol‐2‐ylidene]silver(I) acetate (4a), [4,5‐dichloro‐1,3‐bis(4‐methoxybenzyl)imidazol‐2‐ylidene]silver(I) acetate (4b), [1,3‐bis(4‐methoxybenzyl)benzimidazol‐2‐ylidene]silver(I) acetate (4c), (1,3‐dibenzylimidazol‐2‐ylidene)silver(I) acetate (7a), (1,3‐dibenzyl‐4,5‐dichloroimidazol‐2‐ylidene)silver(I) acetate (7b), and (1,3‐dibenzylbenzimidazol‐2‐ylidene)silver(I) acetate (7c), respectively. The NHC precursor 3c, four NHC–silver complexes 4c and 7a–c were characterised by single‐crystal X‐ray diffraction method. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli, and Gram‐positive bacteria Staphylococcus aureus using the Kirby–Bauer disk‐diffusion method. Almost all the NHC–silver complexes have shown high antibacterial activity compared to the NHC precursors. In addition, the NHC–silver complexes had their cytotoxicity investigated through MTT‐based preliminary in vitro testing on the Caki‐1 cell lines in order to determine their IC50 values. NHC–silver complexes 4a–c and 7a–c were found to have IC50 values of 7.3 (+/–6), 12.7(+/–3), 25.2 (+/–5), 2.5 (+/–3), 10.8 (+/–4) and 12.5 (+/–4) μM respectively on the Caki‐1 cell line.
Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs.
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