Synthesis of benzimidazole derivatives containing amide bond and biological evaluation as acetylcholinesterase, carbonic anhydrase I and II inhibitors

Acetylcholinesterase (AChE) and carbonic anhydrase I (CA-I) and II (CA-II) are two vital metabolic enzymes. AChE inhibitors are seen as target molecules in drug development studies for Alzheimer's treatment. CA inhibitors are target molecules for treating many diseases from glaucoma to cancer. For this reason, it is crucial to identify new AChE and CA inhibitors. In this study, four benzimidazole acetamide derivatives were synthesized and their inhibition effects were investigated against human erythrocyte carbonic anhydrase I (hCA-I), II (hCA-II), and AChE. IC50 values of 9a-10b were determined in the range of 0.936 to 17.07 µM for AChE. IC50 values of 9a–10b for hCA-I were found as 7.21 µM, 4.72 µM, 6.08 µM, 8.23 µM, respectively. On the other hand, IC50 values of 9a–9b for hCA-II were found as 8.64 µM, 7.07 µM, 4.12 µM, 5.93 µM, respectively. According to IC50 values, 9a–10b molecules exhibited strong inhibition effects for AChE and hCAI, II. Also, Molecular docking studies were carried out to explain the binding interaction of 9a–10b with AChE, hCA-I, and hCA-II. © 202

The Effect of Long Term Use of Inhaled N-Acetylcysteine on Cystic Fibrosis Lung Disease

University of Minnesota M.S. thesis. February 2020. Major: Epidemiology. Advisor: Joanne Billings. 1 computer file (PDF); v, 21 pages.Background: Chronic bacterial infection with thick tenacious secretions characterizes lung disease in cystic fibrosis (CF). Historically, thiol derivatives such as N-acetylcysteine (NAC), administered by inhalation of a nebulized solution, were used as mucolytics in CF, but are currently not recommended because of lack of evidence on their safety and efficacy. Previous studies have only focused on short-term effects of nebulized NAC. Objective: Our objective was to examine the rate of decline in forced expiratory volume in the first second of expiration (FEV1) in children with CF who received inhaled NAC and children who did not. Methods: The study population comprised children with CF who received care at two large, affiliated CF centers. Lung function data was compared between the treated and untreated groups using percent predicted (pp) FEV1. Results: Among 199 children younger than 6 years of age, mean pp FEV1 at age 6 did not differ between 107 children previously treated with NAC versus 92 children who did not receive NAC (P=.07). Use of dornase alfa and hypertonic saline was significantly less in the NAC group (P6 and ≤18 years, the rate of pp FEV1 decline was faster in children who did not receive NAC (slope, −1.47 vs -0.57; P<.001). Mean pp FEV1 at 18 years of age did not differ between 32 children treated with NAC versus 20 children who did not receive NAC (P=.06). No serious adverse events related to NAC treatment were reported. Conclusions: Long-term daily use of inhaled NAC is well tolerated and appears to decrease the rate of decline in pp FEV1 in children with CF. Prospective studies are needed to validate these findings

Solvent-Free Synthesis of Chiral Schiff-Base Ligands Based on Ferrocene under Microwave Irradiation and Application to Enantioselective Nitroaldol (Henry) Reaction

WOS: 000289635300002PubMed ID: 21488104Chiral Schiff-bases 3a-f based on ferrocene were designed and synthesized using solvent-free methods by mixing ferrocene carbaldehyde 1 with amino alcohols and amines 2a-f under microwave irradiation and classical method for the enantioselective nitroaldol (Henry) reaction. The Schiff-bases were obtained in shorter reaction times and improved yield under microwave irradiation method over classical method. The highest enantioselectivity was observed in ligand 3e (95% ee) when CH(2)Cl(2) was used as solvent. Chirality 23: 374-378, 2011. (c) 2011 Wiley-Liss, Inc

Use of o-phenylene dioxydiacetic acid impregnated in Amberlite XAD resin for separation and preconcentration of uranium(VI) and thorium(IV)

The impregnation of o-phenylene dioxydiacetic acid (OPDA) into a polymeric matrix, Amberlite XAD-2000, is reported and was characterized by infrared spectroscopy. The amount of attached OPDA to the polymer resin was found to be 1.77 mmol g(-1) resin. The resin was used for the sorption of U(VI) and Th(IV) from aqueous solution. This sorbent was capable of preconcentrating U(VI) and Th(IV) from weakly acidic or neutral solution. The retained metals were eluted sequentially using 0.25 mol L-1 HCl for U(VI) and I mol L-1 HCl for Th(IV) and determined spectrophotometrically using arsenazo-(III). The capacity of the resin for U(VI) and Th(IV) was found to be 0.121 and 0.113 mmol g(-1), respectively. The impregnated resin exhibits a high chemical stability, reusability and fast equilibration. The method was used for the determination of U(VI) and Th(IV) in synthetic samples and rock samples. (C) 2007 Elsevier B.V. All rights reserved

Solid phase extractive preconcentration of trace metals using p-tert-butylcalix[4]arene-1,2-crown-4-anchored chloromethylated polymeric resin beads

5,11,17,23-Tetrakis(1,1-dimethylethyl)-25,26-dihydroxy-27,28-crown-4-calix[4]arene in the cone conformation was synthesized. This p-tertbutylcalix[4]arene-1,2-crown-4 compound was then anchored with Merrifield chloromethylated resin beads. The modified polymeric resin was characterized by H-1 NMR, FT-IR and elemental analysis and used successfully for the separation and preconcentration of Cu(II), Cd(II), Co(II), Ni(II) and Zn(II) prior to their determination by FAAS. Effective extraction conditions were optimized in both batch and column methods. The resin exhibits good separating ability with maximum between pH 6.0-7.0 for Cu(II), pH 6.0 for Cd(II), pH 5.0 for Co(II), pH 4.0-4.5 for Ni(II), and pH 4.5 for Zn(H). The elution studies were carried out with 0.5 mol L-1 HCL for Cu(II), Co(II) and Co(II), 1.0 mol L-1 HCl for Cd(II) and Zn(II). The sorption capacity, preconcentration factor and distribution coefficient of each metal ion were determined. The detection limits were 1.10, 1.25, 1.83, 1.68 and 2.01 mu g L-1 for Cu(II), Cd(II), Co(II), Ni(II) and Zn(II). The influence of several ions on the resin performance was also investigated. The validity of the proposed method was checked for these metal ions in NIST standard reference material 2709 (San Joaquin Soil) and 2711 (Montana Soil). (c) 2006 Elsevier B.V. All rights reserved

Bilateral diaphragmatic paresis following pediatric liver transplantation

Background: Although diaphragm paresis or paralysis is fairly common following cardiac procedures; it is a less common complication following liver transplantation. Unilateral diaphragm paresis, usually right sided, has been described following liver transplantation in adults and has been rarely described in children. Purpose: Diaphragmatic injury following LT is often unrecognized and is typically unilateral, involving the right hemidiaphragm. Bilateral diaphragm dysfunction following liver transplantation in children is a rare complication. Methods: This is a case report of bilateral diaphragm paresis in a young child following a repeat liver transplantation. Conclusion: Bilateral diaphragm paresis following liver transplantation in children is rare and spontaneous resolution is possible. A conservative approach with noninvasive ventilation as a first line treatment to allow the diaphragm to regain function should be considered

Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction

WOS: 000476767700027Chiral amino boronic acids and their derivatives have a wide range of applications including enzyme inhibitors, anti-cancer agents and molecular sensors. They also draw attention as effective catalysts. Recently, a new proline based amino boronic acid derivative, homoboroproline, was synthesized and demonstrated to be an efficient catalyst in an asymmetric aldol reaction. The reaction mechanism has been elucidated in the present study for the first time. Considering different orientations of the enamine intermediate and the aldehyde, potential alternative mechanisms were modeled with density functional theory (DFT) calculations via PCM/M06-2X/6-31G(d,p) method in acetone. The potential energy surface of each mechanism was explored to establish the rate-determining and enantioselectivity-determining steps. The calculated enantiomeric excess values (>99%) were found to be in agreement with the experimental values (93%, 95%). The detailed investigation of the transition state structures of the selectivity-determining step has revealed that attractive interactions between boron and aldehyde oxygen are responsible for the selectivity confirmed by natural bond orbital (NBO) analysis. The results provide insight into the origin of enantioselectivity in asymmetric aldol reaction catalyzed by homoboroproline.Marmara University, Scientific Research Projects Committee (BAPKO)Marmara University [FEN-B-100615-0269]This work was supported by Marmara University, Scientific Research Projects Committee (BAPKO). Project Number: FEN-B-100615-0269. The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources)

Polymer supported 5,10,15,20-tetrakis(phenoxy acetic acid)porphyrin derivative for separation and preconcentration of d- and f-electron metals

5,10,15,20-tetrakis(phenoxy acetic acid) porphyrin (PAAP) was covalently linked to Merrifield chloromethylated resin. Characterization of PAAP and the modified polymeric matrix were performed by H-1 NMR, FTIR and elemental analysis. The sorbent was used for the separation and enrichment of the d-electron metals (Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)) at pH 6-8 and of the f-electron metals U(VI) and Th(IV) at pH 4-5. The metals ions were preconcentrated with a concentration factor range of 115-215 and then determined by flame atomic absorption spectrometry or visible spectrophotometry using Arsenazo(III). The retained metals were eluted with 2.0 mol L-1 HNO3 in the case of the d-electron metals and 0.1/0.25mol L-1 HCl in the case of the f-electron metals. The procedure was validated by analyzing the NIST standard reference material 2709 (San Joaquin Soil)

Synthesis of novel chiral bisoxazoline ligands with a norbornadiene backbone: use in the copper-catalyzed enantioselective Henry reaction

WOS: 000371304800003Novel chiral bisoxazoline ligands based on norbornadiene were synthesized and used for the asymmetric Henry reaction. Various aromatic aldehydes were converted into chiral beta-nitro alcohols with high yields and moderate to acceptable enantioselectivities under the optimized reaction conditions.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-110T856]We thank the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No. TBAG-110T856) for the financial support

Synthesis of novel chiral bisoxazoline ligands with a norbornadiene backbone: usein the copper-catalyzed enantioselective Henry reaction

Novel chiral bisoxazoline ligands based on norbornadiene were synthesized and used for the asymmetricHenry reaction. Various aromatic aldehydes were converted into chiral-nitro alcohols with high yields and moderateto acceptable enantioselectivities under the optimized reaction conditions.Novel chiral bisoxazoline ligands based on norbornadiene were synthesized and used for the asymmetricHenry reaction. Various aromatic aldehydes were converted into chiral-nitro alcohols with high yields and moderateto acceptable enantioselectivities under the optimized reaction conditions