Synthesis, antimicrobial activity and molecular docking study of benzyl functionalized benzimidazole silver(I) complexes.

In this study, a series of N-functionalized benzimidazole silver(I) complexes were prepared and characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, and elemental analysis. Synthesized N-benzylbenzimidazole silver(I) complexes were evaluated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. The results indicated that N-alkylbenzimidazole silver(I) complexes exhibited good antimicrobial activity compared to N-alkylbenzimidazole derivatives. Especially, complex 2e presented perfect antimicrobial activity than the other complexes. The characterized molecules were optimized by DFT-based calculation methods and the optimized molecules were analyzed in detail by molecular docking methods against bacterial DNA-gyrase and CYP51. The amino acid residues detected for both target molecules are consistent with expectations, and the calculated binding affinities and inhibition constants are promising for further studies. A series of N-alkylbenzimidazole silver(I) complexes were synthesized and fully characterized by means of 1H NMR, 13C NMR, and FT-IR spectroscopies. Synthesized N-alkylbenzimidazole silver(I) complexes were investigated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. All complexes showed better activity according to Ampicilin against Pseudomonas aeruginosa. The molecules which were firstly optimized by DFT-based calculation methods were also analyzed by molecular docking methods against DNA gyrase of E. Coli and CYP51. 338 × 190 mm (96 × 96 DPI).

Design, synthesis, antimicrobial activity and molecular docking study of cationic bis-benzimidazole-silver(I) complexes.

Two series of bis(1-alkylbenzimidazole)silver(I) nitrate and bis(1-alkyl-5,6-dimethylbenzimidazole)silver(I) nitrate complexes, in which the alkyl substituent is either an allyl, a 2-methylallyl, an isopropyl or a 3-methyloxetan-3-yl-methyl chain, were synthesized and fully characterized. The eight N-coordinated silver(I) complexes were screened for both antimicrobial activities against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii) and Gram-positive (Staphylococcus aureus, Staphylococcus aureus MRSA, and Enterococcus faecalis) bacteria and antifungal activities against Candida albicans and Candida glabrata strains. Moderate minimal inhibitory concentrations (MIC) of 0.087 µmol/mL were found when the Gram-negative and Gram-positive bacteria were treated with the silver complexes. Nevertheless, MIC values of 0.011 µmol/mL, twice lower than for the well-known fluconazole, against the two fungi were measured. In addition, molecular docking was carried out with the structure of Escherichia coli DNA gyrase and CYP51 from the pathogen Candida glabrata with the eight organometallic complexes, and molecular reactivity descriptors were calculated with the density functional theory-based calculation methods.

Novel benzimidazol-2-ylidene carbene precursors and their silver(I) complexes: Potential antimicrobial agents.

Novel benzimidazolium salts were synthesized as N-heterocyclic carbene (NHC) precursors, these NHC precursors were metallated with Ag2O in dichloromethane at room temperature to give novel silver(I)-NHC complexes. Structures of these benzimidazolium salts and silver(I)-NHC complexes were characterized on the basis of elemental analysis, (1)H NMR, (13)C NMR, IR and LC-MS spectroscopic techniques. A series of benzimidazolium salts and silver(I)-NHC complexes were tested against standard bacterial strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungal strains: Candida albicans and Candida tropicalis. The results showed that benzimidazolium salts inhibited the growth of all bacteria and fungi strains and all silver(I)-NHC complexes performed good activities against different microorganisms.

Benzimidazolium-based novel silver N-heterocyclic carbene complexes: synthesis, characterisation and in vitro antimicrobial activity.

This study reports the synthesis, characterisation and antimicrobial activity of five novel silver N-heterocyclic carbene (Ag-NHC) complexes obtained by N-propylphthalimide and N-methyldioxane substituted benzimidazolium salts with silver oxide. The reactions were performed at room temperature for 24 h in the absence of light. The obtained complexes were identified and characterised by (1)H and (13)C NMR, FT-IR and elemental analysis techniques. The minimum inhibitory concentration (MIC) of the complexes was determined for E. coli, P. aeruginosa, E. faecalis, S. aureus, C. tropicalis and C. albicans in vitro through agar and broth dilution. The results indicated that these complexes exhibit antimicrobial activity. In particular, complex 3 presented the significant broad spectrum antimicrobial activity.

Synthesis, characterization and antimicrobial activities of novel silver(I) complexes with coumarin substituted N-heterocyclic carbene ligands.

Eight new coumarin substituted silver(I) N-heterocyclic carbene (NHC) complexes were synthesized by the interaction of the corresponding imidazolium or benzimidazolium chlorides and Ag2O in dichloromethane at room temperature. Structures of these complexes were established on the basis of elemental analysis, (1)H NMR, (13)C NMR, IR and mass spectroscopic techniques. The antimicrobial activities of carbene precursors and silver NHC complexes were tested against standard strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungi Candida albicans and Candida tropicalis. Results showed that all the compounds inhibited the growth of the all bacteria and fungi strains and some complexes performed good activities against different microorganisms. Among all the compounds, the most lipophilic complex bis[1-(4-methylene-6,8-dimethyl-2H-chromen-2-one)-3-(naphthalene-2-ylmethyl)benzimidazol-2-ylidene]silver(I) dichloro argentate (5e) was found out as the most active one.

Antioxidant Effect of Ethanolic Extract of Propolis in Liver of L-NAME Treated Rats.

BACKGROUND: The blocking of nitric oxide synthase (NOS) activity may cause vasoconstriction with formation of reactive oxygen species. Propolis is a natural product collected from plants by honeybees. Propolis has biological and pharmacological properties. OBJECTIVES: This study was designed to investigate the effects of propolis on catalase (CAT) activity, nitric oxide (NO) and malondialdehyde (MDA) levels in the liver tissues of NOS inhibited rats by Nω-Nitro-L-arginine methyl ester (L-NAME). MATERIAL AND METHODS: Rats were given a NOS inhibitor (L-NAME, 40 mg/kg, intraperitoneally) for 15 days to provoke hypertension and propolis (200 mg/kg, by gavage) the last 5 of the 15 days. RESULTS: Nitric oxide levels in the liver tissue of the rats given L-NAME significantly decreased (p<0.01). That parameter did not significantly alter in the liver of rats treated with propolis compared to the control group. CAT activity and MDA levels in the liver of the rats administrated L-NAME significantly increased compared to the control group (p<0.01). These parameters significantly decreased in the liver of the rats given L-NAME + propolis compared to the L-NAME group (p<0.01). CONCLUSIONS: The present data shows that L-NAME in the liver may enhance oxidative stress via inhibited nitric oxide synthase. Our results also suggest that this effect is suppressed by the antioxidant properties of propolis in the liver tissue of NOS inhibited rats.

Synthesis, antioxidant and anti-microbial properties of two organoselenium compounds.

The aim of this study is synthesis of two different series of organoselenium compounds and available in vitro antioxidant and antimicrobial properties of these synthetic compounds. The synthetic compounds were identified by (1)H-NMR (300 MHz), (13)C-NMR (75.5 MHz), FT-IR spectroscopic techniques and micro analysis. Antioxidant properties of two synthetic organoselenium compounds were determined by 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical method, reducing power assay and ß-carotene bleaching method as in vitro. Antimicrobial effects of samples were assessed by the agar dilution procedure and using gram positive and gram-negative bacteria and yeast strains. Although 1,3-di-p-methoxybenzylpyrimidine-2-selenone showed better antiradical activity in DPPH test and higher protective activity on ß-carotene, 1-isopropyl-3-methylbenzimidazole-2-selenone was found to be better in reducing power and antimicrobial activity.

Role of propolis on biochemical parameters in kidney and heart tissues against L-NAME induced oxidative injury in rats.

Nitric oxide (NO), produced by endothelial NO synthase, is recognised as a central antiinflammatory and antiatherogenic principle in the vasculature. Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, may improve vascular function by enhancing NO bioavailability. In this article, we investigated antioxidant effects of propolis on biochemical parameters in kidney and heart tissues of acute NO synthase inhibited rats by Nω-nitro-l-arginine methyl ester (l-NAME). There was increase (p < 0.001) in the activities of catalase and malondialdehyde levels in the l-NAME treatment groups when compared with control rats, but NO levels were decreased in both kidney and heart tissues. There were statistically significant changes (p < 0.001) in these parameters of l-NAME + propolis treated rats as compared with l-NAME-treated group. In summary, propolis may influence endothelial NO production.

Modulating effects of selenium in adrenal medulla of rats exposed to 7,12-dimethylbenz[a]anthracene.

OBJECTIVE: The aim of this study was to evaluate the chemopreventive potential of organoselenium compounds (Se I and Se II) in the well-established rat model treated with 7,12-dimethylbenz[a]anthracene (DMBA), by monitoring the extent of tyrosine hydroxylase (TH) activity, adrenomedullin (ADM) level and total RNA level in adrenal medulla. Organic pollutants are the most important environmental factor for the biologic systems. DMBA exposure appears to be associated with a number of physiological disease processes. METHODS: The effects of Se I and Se II compounds were investigated on TH activity, ADM and total RNA levels in adrenal medulla of rats exposed to DMBA. RESULTS: TH activity, ADM and total RNA levels were found to be increased significantly due to the effect of DMBA (p < 0.05). This increase was restricted in the Se I- and Se II-treated groups (p < 0.05). CONCLUSION: The present data showed that the organoselenium compounds may have important effects in the maintainance of homeostasis against stress induced by DMBA.

Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats.

The objective of current study is to investigate the effects of the administration of chrysin (CH) and quercetin (Q) on rat liver in which oxidative and histological damage had been induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were randomly divided into six equal groups. TCDD was orally administered at the dose of 2 µg/kg/week, and Q and CH were orally administered at the doses of 20 mg/kg day and 50 mg/kg/day, respectively, by gavages dissolved in corn oil. The liver samples to be analyzed for the determination of oxidative and histological alternations were taken from rats at 60 days. The results indicated that although 2,3,7,8-TCDD significantly induced (P ≤ 0.01) lipid peroxidation (increase of MDA levels), it positively affected oxidant/antioxidant system (a decline in the levels of GSH, CAT, GSH-Px, and CuZn-SOD) in rats significantly. The histological changes observed in the liver correlated with the biochemical findings. However, these effects of TCDD on oxidative and histological changes were eliminated by Q and CH treatment. In conclusion, TCDD caused an adverse effect on rat's liver. When Q and CH were given together with TCDD, they prevented hepatotoxicty induced by TCDD. Thus, it is thought that Q and CH may be useful as a new category of anti-TCDD toxicity agent.

Role of propolis on oxidative stress in fish brain.

INTRODUCTION: Cypermethrin causes its neurotoxic effect through voltage-dependent sodium channels and integral protein ATPases in the neuronal membrane. Brain and nerve damage are often associated with low residual level of pesticides. In vitro and in vivo studies have also shown that pesticides cause free radical-mediated tissue damage in brain. Propolis has antioxidant properties. The main chemical classes found in propolis are flavonoids and phenolics. Bioflavonoids are antioxidant molecules that play important roles in scavenging free radicals, which are produced in neurodegenerative diseases and aging. METHODS: To determine the protective role of propolis, rainbow trouts were treated with cypermethrin, followed by biochemical analyses of brain tissue. Fish were divided into four groups: control, propolis-treated, cypermethrin-treated, and cypermethrin + propolis-treated. RESULTS: In fish brains, catalase (CAT) activity decreased (P ≤ 0.001) and malondialdehyde (MDA) level increased (P ≤ 0.001) in cypermethrin-treated group compared to control group. In cypermethrin + propolis-treated group CAT activity increased (P ≤ 0.001) and MDA level decreased (P ≤ 0.001) compared to cypermethrin group. DISCUSSION: The results demonstrated that the negative effects, observed as a result of cypermethrin treatment, could be reversed by adding supplementary propolis. Propolis may improve some biochemical markers associated with oxidative stress in fish brain, after exposure to cypermethrin.

Role of propolis on tyrosine hydroxylase activity and blood pressure in nitric oxide synthase-inhibited hypertensive rats.

Reduction in the synthesis or bioavailability of nitric oxide plays a significant role in the development of hypertension. Propolis is a resinous product collected by honeybees from various plant sources. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines. The aim of this study was to examine the effect of propolis on blood pressure (BP), TH, and total RNA levels in the adrenal medulla, heart, and hypothalamus tissues in chronic nitric oxide synthase (NOS)-inhibited rats by N(w)-nitro-l-arginine methyl ester (L-NAME). Rats received NOS inhibitor (L-NAME) for 15 days to produce hypertension and propolis for the last 5 days. TH activity and total RNA levels significantly increased in adrenal medulla, heart, and hypothalamus tissues in L-NAME-treated groups (P < .05). TH activity and total RNA levels of L-NAME+propolis-treated rats reduced (P < .05) compared with L-NAME-treated groups. TH activity in propolis-treated rats was reduced to the control values. L-NAME led to a significant increase in BP compared with the control group. Propolis administration to L-NAME-treated rats reduced BP but this was not statistically significant compared to L-NAME-treated groups. These results suggest that propolis decreases TH activity in NOS-inhibited hypertensive rats and thereby may modulate the synthesis of catecholamine and BP.

Ameliorating effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced nephrotoxicity in rats.

The aim of this study is to investigate the beneficial effects of the quercetin (Q) and chrysin (CH) against nephrotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental contaminant, in rats. Rats were divided randomly into six equal groups. TCDD, Q and CH were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, 20 mg/kg/day and 50 mg/kg/day, respectively. The kidney samples were taken from all rats on day 60 for the determination of thiobarbituric acid reactive substances (TBARS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels by spectrophotometric method. The results indicated that TCDD significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, Q and CH significantly prevented toxic effects of TCDD via increased GSH, CAT, GPx and SOD levels but decreased formation of TBARS. Also, it was determined that exposure to TCDD leads to significant histological damage in kidney tissue, and these effects can be eliminated with Q and CH treatment. In conclusion, the current study showed that exposure to TCDD can exert nephrotoxicity in rats. When Q and CH were given together with TCDD, they prevented nephrotoxic effects of TCDD. Their preventive effect lends more support to the role of oxidative and histological damage in the overall toxicity of TCDD.

The determination of oxidative damage in heart tissue of rats caused by ruthenium(II) and gold(I) N-heterocyclic carbene complexes.

In the present study, we aimed to determine the oxidative damage in rat heart tissue induced by ruthenium(II)-NHC (Ru) and gold(I)-NHC (Au) complexes which have anticarcinogenic effects and not used clinically yet. For this purpose, 35 Sprague-Dawley rats were randomly divided into 5 equal groups. In the control group, rats treated with saline, Ru and Au complexes were intraperitoneally given high (10 mg/kg) and low (5 mg/kg) doses as only one administration. The animals were killed, and heart tissues were taken on day 10 of the drug administration for the determination of the biochemical parameters (malondialdehyde, superoxide dismutase, reduced glutathione and catalase levels). It was determined that both Ru and Au complexes treatment significantly caused oxidative damage compared to the control group. Additionally, it was shown that Au treatment caused more adverse effects than Ru treatment. Also, it was clearly found that the occurred effects were generally determined in a dose-dependent manner. In conclusion, when these compounds synthesized for the treatment of cancer were used, they caused oxidative damage in heart tissue. However, Ru complex could be preferred for cancer treatment in terms of user safety.

Antioxidative effects of curcumin, ß-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver.

The aim of this study was to investigate the effectiveness of curcumin, ß-myrcene (myrcene) and 1,8-cineole (cineole) on antioxidant defense system in rats given a persistent environmental pollutant (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD). Rats (n = 112) were divided randomly into 8 equal groups. One group was kept as control and given corn oil as carrier. TCDD was orally administered at the dose of 2 µg/kg/week. Curcumin, myrcene and cineole were orally administered at the doses of 100 mg/kg/day, 200 mg/kg/day and 100 mg/kg/ day, respectively, by gavages dissolved in corn oil with and without TCDD. The liver samples were taken from half of all rats on day 30 and from the remaining half on day 60 for the determination of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and CuZn-SOD levels by spectrophotometric method. The results indicated that although TCDD significantly (p ≤ 0.01) increased formation of TBARS, it caused a significant decline in the levels of GSH, CAT, GSH-Px and CuZn-SOD in rats. In contrast, curcumin, myrcene and cineole significantly increased GSH, CAT, GSH-Px and CuZn-SOD levels but decreased formation of TBARS. Additionally, the antioxidative effects of curcumin, myrcene and cineole were increased at day 60 compared to day 30. In the TCDD groups given curcumin, myrcene and cineole, oxidative stress decreased by time. In conclusion, curcumin, myrcene and cineole showed antioxidant activity and eliminated TCDD-induced oxidative stress in rats in a time-dependent manner.

Protective effects of quercetin and chrysin against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress, body wasting and altered cytokine productions in rats.

The aim of this study is to investigate the effects of the quercetin (Q) and chrysin (CH) on oxidative stress, cytokines levels and body weights in rats induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into six equal groups. TCDD, Q and CH were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, 20 mg/kg/day and 50 mg/kg/day, respectively. The blood samples were taken from all rats at 60th days to be analyzed for the determination of thiobarbituric acid reactive substances (TBARS), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The results indicated that although TCDD increased significantly TBARS and TNF-α levels, it caused a decline in the levels of IFN-γ and body weight. In contrast, these effects of TCDD on TBARS, TNF-α, IFN-γ levels and body weight were significantly prevented by treatments of Q and CH. In conclusion, it was determined that TCDD caused the adverse effects on immune functions, body weight and oxidative stress in rats. However, Q and CH administered with TCDD eliminated these adverse effects. These results suggest that Q and CH may play a protective role against TCDD toxicity.

Novel platinum-N-heterocyclic carbene complex is more cardiotoxic than cis-platin in rats.

Cis-platin and other platinum complexes are important chemotherapeutic agents useful in the treatment of several cancers. However, therapeutic usage of cis-platin and other platinum complex are limited by their undesirable side effects including cardiotoxicity. In this context, we aimed to compare the damage caused in heart by cis-platin and novel platinum-N-heterocyclic carbene (Pt-NHC) complex. For this purpose, 35 Sprague-Dawley rats were divided randomly into five equal groups (n = 7 for each group). Cis-platin and novel Pt-NHC complex were intraperitoneally administered at a single dose of 5 mg/kg and 10 mg/kg and then sacrificed 10 days after this treatment. The heart tissues were taken from all rats for determination of oxidative and myocardial damage. Cis-platin and novel Pt-NHC complex caused oxidative and histological damage in the heart tissue in a dose-dependent manner (p < 0.05). On the other hand, at the same dose levels, cis-platin caused lower oxidative and histological damage in heart tissue compared to novel Pt-NHC complex. These results suggest that novel Pt-NHC complex is more cardiotoxic than cis-platin.

Gold(I) complexes of N-heterocyclic carbene ligands containing benzimidazole: synthesis and antimicrobial activity.

Gold(I) N-heterocyclic carbene (NHC) complexes were obtained in good yields from the corresponding silver complexes by treatment with [AuCl(PPh3)] following the commonly used silver carbene transfer route. The silver complexes were synthesized from the benzimidazolium halide salts by the in situ reactions with Ag2O in dichloromethane as a solvent at room temperature. All gold complexes have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. Au-NHC complexes were evaluated for their in vitro antimicrobial activity against a variety of Gram-positive and Gram-negative bacteria and fungal species.

Synthesis and antimicrobial activity of novel Ag-N-hetero-cyclic carbene complexes.

A series of imidazolidinium ligand precursors are metallated with Ag2O to give silver(I) N-heterocyclic carbene complexes. All compounds were fully characterized by elemental analyses, 1H-NMR, 13C-NMR and IR spectroscopy techniques. All compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and the fungi Candida albicans and Candida tropicalis. The new imidazolidin-2-ylidene silver complexes have been found to display effective antimicrobial activity against a series of bacteria and fungi.

Role of selenium compounds on tyrosine hydroxylase activity, adrenomedullin and total RNA levels in hearts of rats.

Synthetic organoselenium compounds can be tailored to achieve greater chemopreventive efficacy with minimal toxic side effects by structural modifications. Two organoselenium compounds (Se I and Se II) were synthesized and evaluated for their antihypertensive and therapeutic properties by adrenomedullin (ADM) levels and tyrosine hydroxylase (TH) activity assays in rat heart tissue. 7,12-Dimethylbenz[a]anthracene (DMBA) is known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. TH is thought to be a rate-limiting enzyme in the biosynthesis of catecholamines. ADM, a potent endogenous vasodilating and natriuretic peptide, may play an important role in the pathophysiology of chronic heart failure. The effects of Se I and Se II were investigated on TH activity, ADM and total RNA levels in the hearts of albino Wistar rats. TH activity was found to be increased significantly by the effect of DMBA (P<0.05). This increase was restricted in the Se I and Se II treated groups. ADM level was found to be decreased insignificantly by the effect of DMBA (P>0.05). Total RNA level was found to be decreased significantly by the effect of DMBA (P<0.05). This study demonstrates that synthetic organoselenium compounds can regulate DMBA-induced stress related changes in rat heart.