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N-heterocyclic carbene (NHC) based compounds are remarkably known for astonishing biological potentials. Coordination of metal center with these compounds can substantially improve the biological potential for better efficacy. In this context, three binuclear azolium salts (L1-L3) and subsequent selenium adducts L1Se-L3Se were synthesized and assured through analytical techniques. Synthesized compounds were also simulated through computational approach and results were compared with experimental observations that also relatable with biological potentials. Synthesized compounds were screened against bacterial strains and interestingly, the studied compounds showed good antimicrobial potential with MIC values of 7.01, 10.7 and 10.5 µM for S. Aureus (gram positive bacteria) while 12.5, 11.75 and 14.5 µM against E. Coli (gram negative bacteria). The studied compounds showed good antioxidant activity to scavenge DPPH free radicals among which azolium salts were found better in antioxidant potential (IC 50 5.75-6.55 µg/mL) than their respective selenium compounds (IC 50 9.50-12.75 µg/mL). The hemolytic assay against red blood cells showed that ligands are least toxic comparative to their Se-adducts and can be further trialed for In Vivo studies., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict on interest in publishing the scientific findings in the submitted manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study, Raman spectroscopy is employed to analyze and characterize two salts (N-heterocyclic carbene) and their respective selenium N-heterocyclic carbene compounds. The features observed as differences among Raman spectral data of two different N-heterocyclic carbene salts are called Salt-I and Salt-II and their respective Se compounds, called Compound-I & Compound-II, are used to confirm the formation covalent bond between Se atom carbon atom of carbene. Enhancement in peak intensities and shifting of peak positions is directly related with compound formation. Raman spectral data provide a detail information about bond formation, chemical and structural differences between salts and compounds. The observed Raman spectral features of both salts and compounds are in consistent with computationally calculated Raman spectral features. Raman spectral features of each salt and its respective compound was further analyzed with principal component analysis, which was found helpful for differentiating each salt from its respective compound., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Benzimidazolium salts (3-6) were synthesized as stable N-Heterocyclic Carbene (NHC) precursors and their selenium-NHC compounds/Selenones (7-10) were prepared using water as a solvent. Characterization of each of the synthesized compounds was carried out by various analytical and spectroscopic (FT-IR, 1 H-, 13 C NMR) methods. X-ray crystallographic analyses of single crystals obtained for salts 3 and 5 were carried out. Synthesized salts and their Se-NHCs were tested in-vitro for their anticancer potential against Cervical Cancer Cell line from Henrietta Lacks (HeLa), Breast cancer cell line (MDA-MB-231), Adenocarcinoma cell line (A549) and human normal endothelial cell line (EA.hy926). MTT assay was used for analysis and compared with standard drug 5-flourouracil. Benzimidazolium salts (3-6) and their selenium counter parts (7-10) were found potent anticancer agents. Salt 3-5 were found to be potent anticancer against HeLa with IC 50 values 0.072, 0.017 and 0.241 μM, respectively, which are less than standard drug (4.9 μM). The Se-NHCs (7-10) had also shown significant anticancer potential against HeLa with IC 50 values less than standard drug. Salts 3, 4 against EA.hy926, compounds 3,5,6, and 10 against MDA-MB-321, and compounds 4, 10 against A-549 cell line were found more potent anticancer agents with IC 50 values less than standard drug. Molecular docking for (7-10) showed their good anti-angiogenic potential having low binding energy and significant inhibition constant values with VEGFA (vascular endothelial growth factor), EGF (human epidermal growth factor), COX1 (cyclooxygenase-1) and HIF (hypoxia inducible factor)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The current study was conducted to evaluate the antimicrobial, antioxidant, antileishmanial and cytotoxic potential of designed derivatives of 1,1'-(1,3-phenylenebis(methylene))bis(3-alkyl/aryl-1H-benzimidazol-3-ium) salts. The antibacterial potential of the test compounds was investigated against Staphylococcus aureus, Pseudomonas aeruginosa and two methicillin-resistant S. aureus (MRSA) strains (MRSA10, MRSA11), where compound 6 showed the best results. For brine shrimp lethality bioassay (BSLB), compound 6 again showed up to 100% mortality at 200 μg/mL and 56.7% mortality at 6.25 μg/mL. Antileishmanial assay was performed against Leishmania tropica at 20 μg/mL dosage, where 6 showed the most promising activity with 16.26% survival (83.74% mortality; IC50=14.63 μg/mL). The anticancer potential of the selected benzimidazole derivatives was evaluated against two selected cell lines (human colorectal cancer, HCT-116 and breast adenocarcinoma, MCF-7) using sulforhodamine B (SRB) assay. Compound 6 was found to be the most effective cytotoxic compound with 75% inhibition of HCT-116 proliferation at 1 mg/mL concentration. Succinctly, 6 exhibited impressive pharmacological potential that might be attributed to its higher lipophilic character owing to the longer N-substituted alkyl chains when compared to the other test compounds.

The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A series of benzimidazole-based N-heterocyclic carbene (NHC) proligands {1-benzyl-3-(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (1/4), 1,3-bis(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (2/5) and 1,3-bis(3-(2-methylbenzyl)-benzimidazolium-1-ylmethylbenzene dibromide/dihexafluorophosphate (3/6)} has been synthesized by the successive N-alkylation method. Ag complexes {1-benzyl-3-(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (7), 1,3-bis(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (8) and 1,3-bis(3-(2-methylbenzyl)-benzimidazol-2-ylidene)-1-ylmethylbenzene disilver(I) dihexafluorophosphate (9)} of NHC ligands have been synthesized by the treatment of benzimidazolium salts with Ag2O at mild reaction conditions. Both, NHC proligands and Ag-NHC complexes have been characterized by (1)H and (13)C{(1)H} NMR and FTIR spectroscopy and elemental analysis technique. Additionally, the structure of the NHC proligand 5 and the mononuclear Ag complexes 7 and 8 has been elucidated by the single crystal X-ray diffraction analysis. Both the complexes exhibit the same general structural motif with linear coordination geometry around the Ag centre having two NHC ligands. Preliminary in vitro antibacterial potentials of reported compounds against a Gram negative (Escherichia coli) and a Gram positive (Bacillus subtilis) bacteria evidenced the higher activity of mononuclear silver(I) complexes. The anticancer studies against the human derived colorectal cancer (HCT 116) and colorectal adenocarcinoma (HT29) cell lines using the MTT assay method, revealed the higher activity of Ag-NHC complexes. The benzimidazolium salts 4-6 and Ag-NHC complexes 7-9 displayed the following IC50 values against the HCT 116 and HT29 cell lines, respectively, 31.8 ± 1.9, 15.2 ± 1.5, 4.8 ± 0.6, 10.5 ± 1.0, 18.7 ± 1.6, 1.20 ± 0.3 and 245.0 ± 4.6, 8.7 ± 0.8, 146.1 ± 3.1, 7.6 ± 0.7, 5.5 ± 0.8, 103.0 ± 2.3 μM., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The article describes syntheses and characterizations of carbonyl functionalized benzimidazolium salts, I–IV . While salts I–III are unstable at room temperature, salt IV remained stable and was further utilised to form N -heterocyclic carbene (NHC) compounds of silver(I), V and VI , and selenium compound, VII respectively. Compounds IV–VII were tested for their antibacterial potential against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). Salt IV shows a very low inhibition potential (minimum inhibitory concentration, MIC 500 μg/mL) compared to the respective silver(I)-NHC, V and VI (MIC 31.25 μg/mL against both, E. coli and S. aureus ) and selenium compound, VII (MIC 125 μg/mL against E. coli and 62.50 μg/mL against S. aureus ). In DNA cleavage abilities, all the test compounds cleave DNA in which the VII cleaves the DNA at the faster rate. Meanwhile, the silver(I)-NHC complexes V and VI act at the same mode and pattern of DNA cleavage while VII is similar to IV . [ABSTRACT FROM AUTHOR]

Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)–NHC complexes (NHC = N -heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt ( II ) and respective Ag(I)–NHC complex ( III ) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II . Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities. [ABSTRACT FROM AUTHOR]

This manuscript describes synthesis, spectral (FT-IR and NMR), and structural studies of a newpara-xylyl linkedbis-imidazolium salt (1) and the dinuclear Ag(I)–N-heterocyclic carbene complex (2). Both1and2were tested for their potential against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines. According to cell viability measurements using MTT assay, the test compounds showed dose-dependent cytotoxic activities against both cell lines. The complex displayed significant activity (IC50 = 20.9 μM for HCT 116 and 2.4 μM for MCF-7) compared to their respective imidazolium salt (IC50 > 200 μM for HCT 116 and  = 137 μM for MCF-7). The photomicrographs of the cells treated with2revealed that the cytotoxic efficacy of2is mainly by deposition of silver in the cytoplasm of the affected cells since clear signs of black silver deposits in the cytoplasm of the affected cells were observed. [ABSTRACT FROM AUTHOR]

Background: Since the first successful synthesis of Ag(I)-N-heterocyclic carbene complex in 1993, this class of compounds has been extensively used for transmetallation reactions where the direct synthesis using other metal ions was either difficult or impossible. Initially, silver(I)-NHC complexes were tested for their catalytic potential but could not get fame because of lower potential compare to other competent compounds in this field; however, these compounds proved to have vital antimicrobial activities. These encouraging biomedical applications further convinced researchers to test these compounds against cancer. The current work has been carried out with this aim. Results: N-ipropylbenzimidazole was synthesized by reaction of benzimidazole with ipropyl bromide. The subsequent treatment of the resulting N-alkylbenzimidazole with ortho/meta/para-(bromomethylene) benzene afforded corresponding bis-benzimidazolium bromides (5-7). The counter anion (Br-) of each salt was replaced by hexaflourophosphate (PF6-)for the ease of handling and further purification (8-10). Each salt (Ligand), in halide form, was further allowed to react with Ag2O with stirring at room temperature for a period of two days to synthesize dinuclear Ag(I)-NHC complexes (11-13). All synthesized compounds were characterized by spectroscopic techniques and microanalysis. Molecular structures of compounds 5, 9 & 10 were established through single crystal x-ray diffraction technique. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116). Results showed that the ligands (5-10) showed mild to negligible cytotoxicity on HCT 116 cells whereas respective silver complexes (11-13) exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 9.7 to 44.5 µM. Interestingly, the complex 13 having para-xylyl spacer was found the most active (IC50 9.7 µM) that verifies our previously reported results. Conclusions: All the bis-benzimidazolium salts (8-10) were found inactive whereas after bonding with silver cations, the Ag(I)-NHC complexes (11-13) showed a dose dependent cytotoxic activity. This proved that silver practice an important role in death of cancer cells. Also, the N-alkyl/aryl substitutions and ortho/metal/para xylyl units regulate the cytotoxicity. [ABSTRACT FROM AUTHOR]