Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors.

Many studies have been conducted on the selective inhibition of human monoamine oxidase B (hMAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications on BB-4h, which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds 4i and 4t achieved IC50 values of 0.041 ± 0.001 µM and 0.065 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition by compounds 4i and 4t was studied using Lineweaver-Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds 4i and 4t were found to be non-toxic. Molecular docking studies were also carried out for compound 4i, which was found as the most potent agent, within hMAO-B catalytic site.

Synthesis, characterization and carbonic anhydrase I and II inhibitory evaluation of new sulfonamide derivatives bearing dithiocarbamate.

In this study, novel dithiocarbamate-sulfonamide derivatives (3a-3k) were synthesized to investigate their inhibitory activity on purified human carbonic anhydrase (hCA) I and II. The IC50 and Ki values of the compounds were calculated to compare their inhibition profiles on hCA I and II isoenzymes. Acetazolamide was used as the standard inhibitor in the enzyme inhibition assay. Compounds 3a, 3e, 3g, 3h, 3j and 3k showed notable inhibitory effects against hCA I and II. Among these compounds, compound 3h was found to be the most active derivate against both the hCA I and II enzymes with Ki values of 0.032 ± 0.001 µM and 0.013 ± 0.0005 µM, respectively. The cytotoxicity of compounds 3a, 3e, 3g, 3h, 3j and 3k toward NIH/3T3 (mouse embryonic fibroblast cell line) was observed and the compounds were found to be non-cytotoxic. Furthermore, molecular docking studies were performed to investigate the interaction types between compound 3h and the hCA I and II enzymes. As a result of this study a novel and potent class of CA inhibitors with good activity potential were identified.

Synthesis, molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives.

New sulfonamide-hydrazone derivatives (3a-3n) were synthesized to evaluate their inhibitory effects on purified human carbonic anhydrase (hCA) I and II. The inhibition profiles of the synthesized compounds on hCA I-II isoenzyme were investigated by comparing their IC50 and Ki values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide, AZA) has also been used as a standard inhibitor. The compound 3e demonstrated the best hCA I inhibitory effect with a Ki value of 0.1676 ±â€¯0.017 µM. Besides, the compound 3m showed the best hCA II inhibitory effect with a Ki value of 0.2880 ±â€¯0.080 µM. Cytotoxicity of the compounds 3e and 3m toward NIH/3T3 mouse embryonic fibroblast cell line was observed and the compounds were found to be non-cytotoxic. Molecular docking studies were performed to investigate the interaction types between active compounds and hCA enzymes. Pharmacokinetic profiles of compounds were assessed by theoretical ADME predictions. As a result of this study a novel and potent class of CA inhibitors were identified with a good activity potential.

Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds.

Discovery of novel anticandidal agents with clarified mechanisms of action, could be a rationalist approach against diverse pathogenic fungal strains due to the rise of resistance to existing drugs. In support to this hypothesis, in this paper, a series of benzimidazole-oxadiazole compounds were synthesized and subjected to antifungal activity evaluation. In vitro activity assays indicated that some of the compounds exhibited moderate to potent antifungal activities against tested Candida species when compared positive control amphotericin B and ketoconazole. The most active compounds 4h and 4p were evaluated in terms of inhibitory activity upon ergosterol biosynthesis by an LC-MS-MS method and it was determined that they inhibited ergosterol synthesis concentration dependently. Docking studies examining interactions between most active compounds and lanosterol 14-α-demethylase also supported the in vitro results.

Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Potent Antifungal Agents.

With the goal of obtaining a novel bioactive compound with significant antifungal activity, a series of 1,3,4-thiadiazole derivatives (3a⁻3l) were synthesized and characterized. Due to thione-thiol tautomerism in the intermediate compound 2, type of substitution reaction in the final step was determined by two-dimensional (2D) NMR. In vitro antifungal activity of the synthesized compounds was evaluated against eight Candida species. The active compounds 3k and 3l displayed very notable antifungal effects. The probable mechanisms of action of active compounds were investigated using an ergosterol quantification assay. Docking studies on 14-α-sterol demethylase enzyme were also performed to investigate the inhibition potency of compounds on ergosterol biosynthesis. Theoretical absorption, distribution, metabolism, and excretion (ADME) predictions were calculated to seek their drug likeness of final compounds. The results of the antifungal activity test, ergosterol biosynthesis assay, docking study, and ADME predictions indicated that the synthesized compounds are potential antifungal agents, which inhibit ergosterol biosynthesis probably interacting with the fungal 14-α-sterol demethylase.

Treatment of vinegar industry wastewater by electrocoagulation with monopolar aluminum and iron electrodes and toxicity evaluation.

We present electrocoagulation (EC) treatment results of vinegar industry wastewater (VIW) using parallel plate aluminum and iron electrodes, and analyze the toxicity of the treatment processes. Due to the chemical complexity of vinegar production wastewater, several parameters are expected to alter the treatment efficiency. Particularly, current density, initial pH, Na2SO4 as support electrolyte, polyaluminum chloride (PAC) and kerafloc are investigated for their effects on chemical oxygen demand (COD) removal. Following several treatment experiments with real wastewater samples, aluminum-plate electrodes were able to reach to a removal efficiency of 90.91% at pH 4, 10 mg/L PAC and an electrical current density of 20.00 mA/cm2, whereas iron-plate electrodes reached to a removal efficiency of 93.60% at pH 9, 22.50 mA/cm2 current density. Although EC processes reduce COD, the usefulness of the system may not be assessed without considering the resultant toxicity. For this purpose, microtox toxicity tests were carried out for the highest COD removal case. It was observed that the process reduces toxicity, as well as the COD. Consequently, it is concluded that EC with aluminum and iron electrodes is COD removal-wise and toxicity reduction-wise a plausible method for treatment of VIW, which has high organic pollutants.

Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates.

In the present study, nineteen new fluoro-benzimidazole derivatives, including nifuroxazide analogs, were synthesized by microwave-supported reactions and tested against a panel of pathogenic microorganisms consisting of resistant strains. The synthesized compounds were characterized and identified by FT-IR, 1H- and 13C-NMR, mass spectroscopy, and elemental analyses, respectively. In vitro antimicrobial and cytotoxic effects of the synthesized compounds were determined by microdilution and by [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] (MTT) assay. The compound 4-[5(6)-fluoro-1H-benzimidazol-2-yl)-N'-(2- methylbenzylidene)]benzohydrazide (18) showed particularly high inhibitory activity against the gastro-intestinal pathogens, such as Escherichia coli O157:H7, Escherichiacoli ATCC 8739, Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 13311 standard strains, with minimum inhibitory concentrations (MIC90) ranging from 0.49-0.98 µg/mL. The microbial panel contained a total of ten pathogens including Klebsiella sp., Mycobacterium sp., MRSA, etc., for which the level of inhibitory activity measured was higher than that exhibited by the tested concentrations (MIC > 1000 µg/mL). In vitro cytotoxicity results revealed that the inhibitory concentration (IC50) value (210.23 µg/mL) of compound 18 against CCD 841 CoN cells (human intestinal epithelial cell line) is about 430 times higher than its MIC90 value against the tested Escherichia coli strains. Furthermore, the docking study of compound 18 suggested that its structure is very compatible with the active site pocket of the phosphofructokinase-2 enzyme.

Electrocoagulation of synthetically prepared waters containing high concentration of NOM using iron cast electrodes.

The aim of this investigation is to evaluate the treatability of synthetically prepared water with high concentration of humic substances by electrocoagulation in batch mode using iron cast electrodes. Effects of applied potential, initial humic substance concentration and supporting electrolyte type on humic substance removal efficiency were investigated. NaNO3, Na2SO4 and NaCl were used as supporting electrolyte. Among these supporting electrolytes, Na2SO4 and NaCl have provided high removal efficiencies, whereas in the experiments using NaNO3 as supporting electrolyte have been observed no flock formation. The highest removal rate is obtainable with NaCl as supporting electrolyte. Removal efficiencies for initial humic substance concentration of 500 mg L-1 with NaCl and Na2SO4 equal to 97.95% for 35 min and 92.69% for 70 min, respectively. This behavior of the system has been derived from oxidation products, available in the bulk solution, of chloride ions. When NaCl is used as supporting electrolyte, there is an advantage of providing the disinfection of water, but humic substances and chloride ions are available in the bulk solution with risk of formation undesirable organo-chlorine compounds, so the Na2SO4 is the most favorable supporting electrolyte.