Iridium(i) complexes bearing hemilabile coumarin-functionalised N-heterocyclic carbene ligands with application as alkyne hydrosilylation catalysts.

A set of iridium(i) complexes of formula IrCl(κC,η2-IRCouR')(cod) or IrCl(κC, η2-BzIRCouR')(cod) (cod = 1,5-cyclooctadiene; Cou = coumarin; I = imidazolin-2-carbene; BzI = benzimidazolin-2-carbene) have beeen prepared from the corresponding azolium salt and [Ir(µ-OMe)(cod)]2 in THF at room temperature. The crystalline structures of 4b and 5b show a distorted trigonal bipyramidal configuration in the solid state with a coordinated coumarin moiety. In contrast, an equilibrium between this pentacoordinated structure and the related square planar isomer is observed in solution as a consequence of the hemilability of the pyrone ring. Characterization of both species by NMR was achieved at the low and high temperature limits, respectively. In addition, the thermodynamic parameters of the equilibrium, ΔHR and ΔSR, were obtained by VT 1H NMR spectroscopy and fall in the range 22-33 kJ mol-1 and 72-113 J mol-1 K-1, respectively. Carbonylation of IrCl(κC,η2-BzITolCou7,8-Me2)(cod) resulted in the formation of a bis-CO derivative showing no hemilabile behaviour. The newly synthesised complexes efficiently catalyze the hydrosilylation of alkynes at room temperature with a preference for the ß-(Z) vinylsilane isomer.

Efficiency enhancement with chloride to iodide ion exchange of benzimidazolium salt as a redox mediator.

The new benzimidazolium derivative (SM-1) salt with ion exchange from the (SM-0) was fabricated and characterized by proton-nuclear magnetic resonance (1H-NMR), carbon-nuclear magnetic resonance (13C-NMR), Fourier-transform infrared spectroscopy (FT-IR), electrospray ionization (EIS-MS), thermal analysis (TG), cyclic voltammetry (CV), and ultraviolet-visible spectroscopy (UV-vis), for electrolytes (liquid or dried) in the DSSC charge transportation mechanism. Also, the influence of ion exchange from chloride to iodine in the synthesized electrolytes, compared to other electrolytes (conventional or commercial), was investigated about DSSC performance efficiency. When using as a liquid electrolyte (SM-1), the power conversion efficiency (ƞ) of the working DSSC device was recorded as 1.980% and it was observed that the performances of DSSCs increased up to 56% when comparing dried electrolyte for SM-1 without conventional redox material (I-/I3 -). In the future, different molecular modifications of this type of benzimidazole derivatives or mixtures with conventional redox couples may further improve the performance of DSSC devices.

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation.

In the present study, coumarin-bearing three pyridinium and three tetra-alkyl ammonium salts were synthesized. The compounds were fully characterized by 1 H- and 13 C-NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco-2) and non-cancer mouse fibroblast (L-929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.

Catechol-bearing imidazolium and benzimidazolium chlorides as promising antimicrobial agents.

Catechol-containing imidazolium (four) and benzimidazolium chlorides (eight) were synthesized to evaluate their antimicrobial properties. All the compounds were fully characterized using 1 H and 13 C nuclear magnetic resonance, liquid chromatography-mass spectrometry, infrared spectroscopic methods, and elemental analyses. Antimicrobial activities of the compounds were tested against the bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, and the fungal strains Candida albicans and Candida glabrata, and promising results were achieved. The two most important benzyl-substituted benzimidazolium chlorides, 3l and 3k, showed comparable activity to vancomycin against MRSA.

Therapeutic potential of coumarin bearing metal complexes: Where are we headed?

The successfully application of some metallodrugs such as salvarsan, silver sulfadiazine and cisplatin in modern medicine launched the biological investigation of organometallic and metal-organic complexes. The availability and tunability of various ligands including N-heterocycles, phosphines, N-heterocyclic carbenes present an extended research area to chemists. In recent years, the preparation of the metal complexes of bioactive organic compounds is a new strategy. Coumarin derivatives are one of the classes of compounds used for this purpose, and many complexes of coumarin derivatives were prepared for enhanced biological activity, especially anticancer and antimicrobial. In this paper, we discuss the current situation of this topic.

Microwave-assisted synthesis of 1-substituted-1H-benzimidazolium salts: Non-competitive inhibition of human carbonic anhydrase I and II.

A series of 1-substituted-1H-benzimidazolium p-toluenesulfonate salts were synthesized in good yields by the reaction of 1-substituted benzimidazole derivatives and p-toluenesulfonic acid under microwave irradiation. Two iodide salts were synthesized by the anion exchange reaction of the corresponding p-toluenesulfonate salt and NaI. All compounds were characterized by 1 H NMR, 13 C NMR, IR, LC-MS spectroscopic methods, and elemental analyses. The crystal structure of 1-methoxyethyl-1H-benzimidazolium p-toluenesulfonate 2d showed that cation and anion are interconnected by N-H···O and C-H···O hydrogen bonds. All compounds were examined as inhibitor of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibit hCA I and hCA II in a non-competitive manner. The iodide salts had higher inhibitory activity than their corresponding p-toluenesulfonate salts.

Some coumarins and benzoxazinones as potent paraoxonase 1 inhibitors.

In this study, we aimed to investigate the effect of some coumarin and benzoxazinone derivatives on the activity of human PON1. Human serum paraoxonase 1 was purified from fresh human serum blood by two-step procedures that are ammonium sulfate precipitation (60-80%) and then hydrophobic interaction chromatography (Sepharose 4B, L-tyrosine and 1-napthylamine). The enzyme was purified 232-fold with a final specific activity of 27.1 U/mg. In vitro effects of some previously synthesized ionic coumarin or benzoxazinone derivatives (1-21) on purified PON1 activity were investigated. Compound 14 (1-(2,3,4,5,6)-pentamethylbenzyl-3-(6,8-dimethyl-2H-chromen-2-one-4-yl))benzimidazolium chloride was found out as the strongest inhibitor (IC50 = 7.84 µM) for PON1 among the compounds. Kinetic investigation and molecular docking study were evaluated for one of the most active compounds (compound 12) and obtained data showed that this compound is competitive inhibitor of PON1 and interact with Leu262 and Ser263 in the active site of PON1. Moreover, coumarin derivatives were found out as the more potent inhibitors for PON1 than benzoxazinone derivatives.

Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies.

Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a-5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 µM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 µM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.

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.

In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1).

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1-20) on purified PON1 activity was investigated. Among these compounds, derivatives 11-20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 µM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis, molecular docking and anticonvulsant studies.

Among many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties. In this study, we prepared fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives and evaluated their hCA inhibitory activities and along with fourteen previously synthesized derivatives we scanned their anticonvulsant effects. As all compounds inhibited purified hCA isoforms I and II, some of them also proved protective against Maximal electroshock seizure (MES) and ScMet induced seizures in mice. Molecular docking studies with selected coumarin derivatives have revealed that these compounds bind to the active pocket of the enzyme in a similar fashion to that previously described for coumarin derivatives.

Evaluation of Microdissection Testicular Sperm Extraction Results in Patients with Non-Obstructive Azoospermia: Independent Predictive Factors and Best Cutoff Values for Sperm Retrieval.

PURPOSE: Testicular sperm extraction (TESE) for intracytoplasmic sperm injection (ICSI) was first introduced for the treatment of non-obstructive azoospermia. This study was conducted to detect predictive factors affecting the success of microTESE. MATERIALS AND METHODS: We retrospectively evaluated the results of 191 cases who underwent microTESE. For each patient, the testicular volume, endocrine profile [follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), total testosterone (TT)], serum inhibin B level, karyotype analysis, and Y chromosome microdeletions were recorded, and all data were analyzed to detect any predictors. The receiver operating characteristic curve, two-sample t-test and regression analysis were used for the statistical analysis. RESULTS: The mean age of the patients was 34.4 ± 5.6 years. Sperm retrieval was successful in 104 (54.5%) patients, and there was no sperm in 87 (45.5%). Seven factors including, testicular size, Johnson score, Y chromosome microdeletion, and serum FSH, LH, FT and TT levels were different between the successful and unsuccessful groups. Six patients had Klinefelter syndrome, and ten patients (5.2%) had a Y chromosome microdeletion (5 AZF-c, 1 AZF-b, 2 AZF-bc, 1 AZF-abc, and 1 AZF-ac). The Johnson score, TT level, family history and Y chromosome microdeletions were determined to be independent predictive factors for sperm found. According to the testicular histology, the sperm-found ratios were 36%, 48.6%, and 95.5% in the sertoli cell only syndrome, maturation arrest, and hypospermatogenesis groups, respectively. CONCLUSION: According to our results, the Johnson score, TT level, family history-related infertility, and Y chromosome microdeletions were determined to be independent predictive factors for sperm found.

New coumarin derivatives as carbonic anhydrase inhibitors.

In the current study, a series of 4-chloromethyl-7-hydroxy-coumarin derivatives containing imidazolium, benzimidazolium, bisbenzimidazolium and quaternary ammonium salts were synthesized, characterized and the inhibition effects of the derivatives on human carbonic anhydrases (hCA I and hCA II) were investigated as in vitro. Structures of these coumarins were confirmed by FT-IR, (1)H NMR, (13)C NMR and LC-MS analyses. Structure activity relationship study showed that 3d (IC50: 79 µM for hCA I and 88 µM for hCA II) performed higher inhibitory activity than others.

Synthesis, characterization, and tyrosinase inhibitory properties of benzimidazole derivatives.

1-Alkylbenzimidazole and 1,3-dialkyl benzimidazolium salts were synthesized and characterized by the data of IR, 1H NMR, 13C NMR spectra and elemental analyses. These compounds were investigated as tyrosinase inhibitors. Tyrosinase has been purified from banana by affinity chromatography on a Sepharose 4B gel conjugated with L-tyrosine-p-aminobenzoic acid. All the synthesized compounds inhibited the tyrosinase activity. Among the compounds studied, 1,4-di(1H-benzo[d]imidazol-1-yl)butane was found to be the most active tyrosinase inhibitor (IC50 0.31 mM).

Synthesis and carbonic anhydrase inhibitory properties of novel coumarin derivatives.

A newly series of water-soluble 1-alkyl-3-(4-methyl-7, 8-dihydroxy-2H-chromen-2-one) benzimidazolium chloride salts (3a-j) were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA) I and II were evaluated. hCA I and II from human erythrocytes were purified by a simple one step procedure by using Sepharose 4B-L-tyrosine-sulphanilamide affinity column. The result showed that all the synthesized compounds were inhibited the CA isoenzymes activity. Among them, 3g and 3j were found to be most active (IC(50) = 22.09 µM and 20.33 µM) for hCA I and hCA II, respectively.

Association of Pb, Cd, and Se concentrations and oxidative damage-related markers in different grades of prostate carcinoma.

Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium (Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development. Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography, and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH. Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and protein carbonyl levels in malign Ca. Blood Pb and tissue Pb were also significantly positively correlated with plasma MDA and protein carbonyl levels in malign Ca. In addition, blood Pb was significantly positively correlated with tissue MDA and protein carbonyl levels in malign Ca, and a significant positive correlation was also found between blood Cd and plasma protein carbonyls and tissue MDA in LGPIN. We observed that altered prooxidant-antioxidant balance and heavy metal levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that changes in the levels of Pb, Cd, Se, MDA, protein carbonyls, and GSH in the blood and/or tissue are related to the prostatic carcinoma development and progression, although triggering one of the mentioned changes is unknown; therefore, further study is required to determine the exact steps of the process and clarify the roles of different substances in order to obtain a more detailed explanation of the phenomenon.

Protective effect of decorin on acute ischaemia-reperfusion injury in the rat kidney.

INTRODUCTION: Transforming growth factor-ß1 (TGF-ß1) has a crucial role in collagen synthesis and fibrosis. TGF-ß1 can be antagonized and/or reduced by the action of certain agents. We propose to identify the role of decorin in treatment of tubular and interstitial fibrosis and in the inhibition of TGF-ß1 in an acute ischaemic kidney. MATERIAL AND METHODS: We grouped 34 female Sprague Dawley type rats into 3 groups as 9 sham, 9 ischaemia-reperfusion (I/R) and 16 I/R + decorin respectively. The rats in the I/R + decorin group had decorin administered intraperitoneally at the dose of 0.1 mg/kg for 9 days after reperfusion. After 9 days, all the rats in the 3 groups were unilaterally nephrectomized. The TGF-ß1 level was measured immunohistochemically in the nephrectomized material. RESULTS: The TGF-ß1 level was lower in the I/R + decorin group. Evaluation of apoptotic activity level by caspase staining showed a statistically significant difference between the 3 groups. The number of caspase stained cells was lower in the I/R + decorin group. The amount of collagen in interstitial tissue was higher in the I/R group than in the I/R + decorin group, but this difference was not statistically significant. CONCLUSIONS: We found that the TGF-ß1 level - the so-called initiator of fibrotic activity - and apoptotic activity were low in the I/R + decorin group. Additional studies must be performed to understand the role of decorin in inhibition of TGF-ß1 and to assess decorin's routine use in acute renal ischaemia.

Does vaginal anti-incontinence surgery affect sexual satisfaction? A comparison of TVT and Burch-colposuspension.

OBJECTIVE: To evaluate the sexual satisfaction rates of women who underwent tension-free vaginal tape (TVT) procedure for stress urinary incontinence and compare it with the results of Burch-colposuspension. MATERIALS AND METHODS: A self-administered questionnaire was given to 81 patients who had undergone TVT or Burch-colposuspension at our institution to determine sexual satisfaction rates and reasons for dissatisfaction. Forty-seven patients in TVT group and 22 patients in Burch-colposuspension group were considered eligible for the study. The mean follow-up period and age of patients in TVT and Burch-colposuspension groups were 34 months, 51.5 years and 89 months, 52.9 years, respectively. The difference between the ages in the two groups was not statistically significant, while the difference between mean follow-up periods was significant (p = 0.000). RESULTS: When evaluating sexual satisfaction, 73% in the TVT group and 86% in the Burch-colposuspension group did not report any difference in sexual satisfaction following surgery, while in the TVT group, 23% expressed negative and 4% positive changes, and in the Burch-colposuspension group 9% expressed negative and 5% positive post surgical changes. The differences in sexual satisfaction rates between the two groups were not considered significant. The majority (54%) of those who expressed a negative change suffered from dyspareunia. CONCLUSIONS: Although sexual satisfaction seems to be more adversely affected by TVT compared to Burch-colposuspension, the difference was not statistically significant. Further studies are required concerning different anti-incontinence techniques in order to arrive at more precise conclusions.

Does vaginal anti-incontinence surgery affect sexual satisfaction? A comparison of TVT and Burch-colposuspension

OBJECTIVE: To evaluate the sexual satisfaction rates of women who underwent tension-free vaginal tape (TVT) procedure for stress urinary incontinence and compare it with the results of Burch-colposuspension. MATERIALS AND METHODS: A self-administered questionnaire was given to 81 patients who had undergone TVT or Burch-colposuspension at our institution to determine sexual satisfaction rates and reasons for dissatisfaction. Forty-seven patients in TVT group and 22 patients in Burch-colposuspension group were considered eligible for the study. The mean follow-up period and age of patients in TVT and Burch-colposuspension groups were 34 months, 51.5 years and 89 months, 52.9 years, respectively. The difference between the ages in the two groups was not statistically significant, while the difference between mean follow-up periods was significant (p = 0.000). RESULTS: When evaluating sexual satisfaction, 73 percent in the TVT group and 86 percent in the Burch-colposuspension group did not report any difference in sexual satisfaction following surgery, while in the TVT group, 23 percent expressed negative and 4 percent positive changes, and in the Burch-colposuspension group 9 percent expressed negative and 5 percent positive post surgical changes. The differences in sexual satisfaction rates between the two groups were not considered significant. The majority (54 percent) of those who expressed a negative change suffered from dyspareunia. CONCLUSIONS: Although sexual satisfaction seems to be more adversely affected by TVT compared to Burch-colposuspension, the difference was not statistically significant. Further studies are required concerning different anti-incontinence techniques in order to arrive at more precise conclusions.

The influence of oxidative damage on viscosity of seminal fluid in infertile men.

Increased oxidative damage has been suggested to play an important role in the viscosity changes of blood. However, changes in levels of oxidative damage products in semen and their relationship to seminal fluid viscosity are unknown. The aim of our study was to investigate whether oxidative damage was associated with seminal plasma viscosity in infertile subjects. The levels of malondialdehyde, and protein carbonyls were measured in sperm and seminal plasma from 102 individuals, including 60 infertile patients. Seminal fluid viscosity and semen viscosity were studied by use of capillary viscometer and glass pipettes, respectively. Significantly higher levels of oxidative stress and damage markers were found in subfertile subjects compared with the control subjects. The seminal fluid viscosities of patients were found to be significantly higher, although all of the control and patient subjects had normal viscoelasticity when semen samples were assessed according to World Health Organization guidelines. From Pearson correlation analysis, there were significant positive correlations between seminal fluid viscosity and seminal malondialdehyde and carbonyl levels in infertile males (r = .676, P < .01; r = .276, P < .05, respectively). Our results suggest that increased oxidative damage might be a factor for hyperviscosity of seminal plasma in infertile males.