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1.
Chem Biodivers ; : e202401021, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954767

RESUMEN

α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-vis, FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4c (IC50= 3.8 µM), 4g (IC50= 14.5 µM), and 4f (IC50= 17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4f and 4h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.

2.
J Biochem Mol Toxicol ; 38(1): e23554, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37855258

RESUMEN

This work includes the synthesis of a new series of palladium-based complexes containing both morpholine and N-heterocyclic carbene (NHC) ligands. The new complexes were characterized using NMR (1 H and 13 C), FTIR spectroscopic, and elemental analysis techniques. The crystal structure of complex 1b was obtained by utilizing the single-crystal X-ray diffraction method. X-ray studies show that the coordination environment of palladium atom is completed by the carbene carbon atom of the NHC ligand, the nitrogen atom of the morpholine ring, and a pair of bromide ligand, resulting in the formation of slightly distorted square planar geometry. All complexes were determined for some metabolic enzyme activities. Results indicated that all the synthetic complexes exhibited powerful inhibitory actions against all aims as compared to the control molecules. Ki values of new morpholine-liganded complexes bearing 4-hydroxyphenylethyl group 1a-e for hCA I, hCA II, AChE, BChE, and α-glycosidase enzymes were obtained in the ranges 0.93-2.14, 1.01-2.03, 4.58-10.27, 7.02-13.75, and 73.86-102.65 µM, respectively. Designing of reported complexes is impacted by molecular docking study, and interaction with the current enzymes also proclaimed that compounds 1e (-12.25 kcal/mol for AChE and -11.63 kcal/mol for BChE), 1c (-10.77 kcal/mol and -9.26 kcal/mol for α-Gly and hCA II, respectively), and 1a (-8.31 kcal/mol for hCA I) are showing binding affinity and interaction from the synthesized five novel complexes.


Asunto(s)
Metano/análogos & derivados , Morfolinas , Paladio , Estructura Molecular , Simulación del Acoplamiento Molecular , Paladio/química , Ligandos , Morfolinas/farmacología
3.
Chem Biodivers ; 20(12): e202301362, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37953698

RESUMEN

This report presents the synthesis and characterization of a range of benzimidazolium salts featuring 3-cyanopropyl groups on the 1st nitrogen atom and varied alkyl groups on the 3rd nitrogen atom within the benzimidazole structure. Benzimidazolium salts were synthesized by N-alkylation of 1-alkyl benzimidazole with 3-cyanopropyl-bromide. The new salts were characterized by 1 H and 13 C-NMR, FT-IR spectroscopic and elemental analysis techniques. In this study, the enzyme inhibition abilities of seven nitrile substituted benzimidazolium salts were investigated against acetylcholinesterase (AChE) and carbonic anhydrase isoenzymes I and II (hCA I and hCA II). They showed a highly potent inhibition effect on AChE, hCA I and hCA II (Ki values are in the range of 26.71-119.09 nM for AChE, 19.77 to 133.68 nM for hCA I and 13.09 to 266.38 nM for hCA II). Reflecting the binding mode of the synthesized cyanopropyl series, the importance of the 2,3,5,6-tetramethylbenzyl, 3-methylbenzyl and 3-benzyl groups for optimal interactions with target proteins, evaluated by molecular docking studies. At the same time, the docking findings support the inhibition constants (Ki ) values of the related compounds in this study. Potential compounds were also evaluated by their pharmacokinetic properties were predicted.


Asunto(s)
Anhidrasas Carbónicas , Anhidrasas Carbónicas/metabolismo , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Sales (Química)/farmacología , Anhidrasa Carbónica II , Espectroscopía Infrarroja por Transformada de Fourier , Inhibidores de la Colinesterasa/química , Anhidrasa Carbónica I , Bencimidazoles , Nitrógeno , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Relación Estructura-Actividad , Estructura Molecular
4.
Chem Biodivers ; 20(5): e202201134, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37052518

RESUMEN

The molecular hybrid approach is very significant to combat various drug-resistant disorders. A simple, convenient, and cost-effective synthesis of thiazole-based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1-(2-phenylthiazol-4-yl)ethanone (3) was used as the main intermediate for the synthesis of 3-(arylidene)-1-(2-phenylthiazol-4-yl)prop-2-en-1-ones (4a-f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achieved via different spectroscopic techniques (UV, FT-IR, 1 H- and 13 C-NMR) and elemental analysis. All synthesized compounds were tested for their α-amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested with in vitro haemolytic assay. All tested compounds showed moderate to excellent α-amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic α-amylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated the in vitro amylase inhibition results, i.e., 3-(3-Methoxyphenyl)-1-(2-phenylthiazol-4-yl)prop-2-en-1-one (4e) exhibited lowest IC50 value 54.09±0.11  µM with a binding energy of -7.898 kcal/mol.


Asunto(s)
Chalcona , Chalconas , Humanos , Relación Estructura-Actividad , Antioxidantes/farmacología , Chalconas/química , Simulación del Acoplamiento Molecular , alfa-Amilasas , Tiazoles/química , Espectroscopía Infrarroja por Transformada de Fourier
5.
Bioorg Chem ; 135: 106513, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37030104

RESUMEN

This work contains synthesis, characterization, crystal structure, and biological activity of a new series of the PEPPSI type Pd(II)NHC complexes [(NHC)Pd(II)(3-Cl-py)]. NMR, FTIR, and elemental analysis techniques were used to characterize all (NHC)Pd(II)(3-Cl-py) complexes. Also, molecular and crystal structures of complex 1c were established by single-crystal X-ray diffraction. Regarding the X-ray studies, the palladium(II) atom has a slightly distorted square-planar coordination environment. Additionally, the enzyme inhibitory effect of new (NHC)Pd(II)(3-Cl-py) complexes (1a-1g) was studied. They exhibited highly potent inhibition effect on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 0.08 ± 0.01 to 0.65 ± 0.06 µM, 10.43 ± 0.98 to 22.48 ± 2.01 µM, 6.58 ± 0.30 to 10.88 ± 1.01 µM and 6.34 ± 0.37 to 9.02 ± 0.72 µM for AChE, BChE, hCA I, and hCA II, respectively). Based on the molecular docking, among the seven synthesized complexes, 1c, 1b, 1e, and 1a significantly inhibited AChE, BChE, hCA I, and hCA II enzymes, respectively. The findings highpoint that (NHC)Pd(II)(3-Cl-py) complexes can be considered as possible inhibitors via metabolic enzyme inhibition.


Asunto(s)
Butirilcolinesterasa , Anhidrasas Carbónicas , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular , Anhidrasas Carbónicas/metabolismo , Estructura Molecular , Inhibidores de Anhidrasa Carbónica/química , Relación Estructura-Actividad
6.
J Biomol Struct Dyn ; 41(21): 11728-11747, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36622368

RESUMEN

Herein, eight new NHC-based selenourea derivatives were synthesized and characterized by using spectroscopic method (1H, 19F, and 13C NMR, FT-IR), and elemental analysis techniques. These compounds were synthesized by mixing benzimidazolium salts, potassium carbonate, and selenium powder in ethyl alcohol. Additionally, the molecular and crystal structures of the three compounds (1c, 2b, and 2c) were determined using the single-crystal x-ray diffraction (XRD) method. Diffraction analysis demonstrated the partial carbon-selenium double-bond character of these compounds. All compounds were determined to be highly potent inhibitors for AChE and XO enzymes. The IC50 values for the compounds were found in the range of 0.361-0.754 µM for XO and from 0.995 to 1.746 µM for AChE. The DNA binding properties of the compounds were investigated. These compounds did not have a remarkable DNA binding property. Also, DPPH radical scavenging activities of the compounds were also investigated. Compounds (1c), (2a), (3a), and (3b) exhibited more pronounced DPPH radical scavenging activity when compared to other compounds. Docking studies were applied by using AutoDock 4 to determine interaction mechanism of the selected compounds (1a), (1b), and (3b). The compound (1b) has good binding affinity (-9.78 kcal/mol) against AChE, and (-6.86 kcal/mol) for XO target. Drug similarity properties of these compounds compared to positive controls were estimated and evaluated by ADMET analysis. Furthermore, molecular dynamics simulations have been applied to understand the accuracy of docking studies. These findings and the defined compounds could be potential candidates for the discovery and progress of effective medicine(s) for AChE and XO in the future.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Compuestos de Selenio , Selenio , Acetilcolinesterasa , Xantina Oxidasa , Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , ADN , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Estructura Molecular
7.
Mol Divers ; 27(6): 2767-2787, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36508118

RESUMEN

Herein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (1H NMR, 13C NMR, 19F NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds' the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with Ki values in the range of 8.30 ± 1.71 to 120.77 ± 8.61 nM for AChE, 16.97 ± 2.04 to 84.45 ± 13.78 nM for hCA I, and 14.09 ± 2.99 to 69.33 ± 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.


Asunto(s)
Inhibidores de la Colinesterasa , Sales (Química) , Sales (Química)/farmacología , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa/metabolismo , Anhidrasa Carbónica I/química , Anhidrasa Carbónica I/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Anhidrasa Carbónica II/química , Anhidrasa Carbónica II/metabolismo , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Estructura Molecular
8.
Chem Biodivers ; 19(12): e202200257, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36260838

RESUMEN

The method for producing 4-trifluoromethoxybenzyl substituted benzimidazolium salts is described in this article. The method is based on the reaction of 4-trifluoromethoxybenzyl substituent alkylating agent with 1-alkylbenzimidazole. This method yielded 1-(4-trifluoromethoxybenzyl)-3-alkylbenzimidazolium bromide salts. These benzimidazolium salts were characterized by using 1 H-NMR, 13 C-NMR, FT-IR spectroscopy, and elemental analysis techniques. The crystal structure of 1f was enlightened by single crystal X-ray diffraction studies. Also, the enzyme inhibition effects of the synthesised compounds were investigated. They demonstrated highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 7.24±0.99 to 39.12±5.66 nM, 5.57±0.96 to 43.07±11.76 nM, and 4.38±0.43 to 18.68±3.60 nM for AChE, hCA I, and hCA II, respectively). In molecular docking study, the interactions of active compounds showing activity against AChE and hCAs enzymes were examined. The most active compound 1f has -10.90 kcal/mol binding energy value against AChE enzyme, and the potential structure compound 1e, which has activity against hCA I and hCA II enzymes, was -7.51 and -8.93 kcal/mol, respectively.


Asunto(s)
Bencimidazoles , Inhibidores de la Colinesterasa , Acetilcolinesterasa/metabolismo , Anhidrasa Carbónica I , Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Bencimidazoles/química , Bencimidazoles/farmacología
9.
Heliyon ; 8(9): e10625, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36185151

RESUMEN

The palladium-based complexes bearing N-heterocyclic carbene (NHC) ligand have long attracted attention as active catalysts for many catalytic reactions. Recently, the biological activities of these complexes, which are stable to air and moisture, have also been wondered. With the aim, we report the synthesis of a series of (NHC)Pd(Br2)(L) complexes (NHC: 1,3-dibenzylbenzimidazolium, L: morpholine, triphenylphosphine, pyridine, 3-chloropyridine, and 2-aminopyridine). All complexes were characterized by NMR (1H and 13C), FTIR spectroscopic and elemental analysis techniques. In addition, the single crystal structures of the complex 3, 4, and 6 were determined through single crystal x-ray crystallographic method. Furthermore, the carbonic anhydrase I and II isoenzymes (hCAs) and acetylcholinesterase (AChE) inhibition effects of these palladium-based complexes bearing NHC ligand were investigated. They showed highly potent inhibition effect with Ki values are between 10.06 ± 1.49-68.56 ± 11.53 nM for hCA I isoenzyme, 7.74 ± 0.66 to 49.39 ± 6.50 nM for hCA II isoenzyme and 22.83 ± 3.21 to 64.09 ± 9.05 nM for AChE enzyme.

10.
Arch Pharm (Weinheim) ; 355(12): e2200276, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35986370

RESUMEN

Five 4-hydroxyphenylethyl substituted pyridine enhanced, precatalyst, preparation, stabilization, and initiation-Pd-N-heterocyclic carbene (PEPPSI-Pd-NHC) complexes are synthesized in a straightforward way. All PEPPSI-Pd-NHC complexes were prepared by mixing 4-hydroxyphenylethyl substituted NHC precursors, palladium chloride, potassium carbonate, and potassium bromide in pyridine. All complexes were screened for human carbonic anhydrase I (hCA I) and hCA II, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase (α-Glu) inhibitory activities. The ChE inhibitory activities of the new PEPPSI-Pd-NHC complexes bearing the 4-hydroxyphenylethyl group (1a-e) against α-Glu, AChE, and BChE were determined by the Tao and Ellman methods. The results indicated that all the synthetic complexes exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. The Ki values of the new PEPPSI-Pd-NHC complexes 1a-e for hCA I, hCA II, AChE, BChE, and α-Glu were obtained in the ranges of 18.98-32.65, 22.95-38.13, 3.67-11.65, 4.09-9.36, 186.92-287.45 µM, respectively. Among the synthesized complexes, the most potent complexes were 1c toward hCA I and II with Ki values 18.98 and 22.95 µM, and 1d toward AChE and BChE with Ki = 3.67 and 4.09 µM, respectively.


Asunto(s)
Acetilcolinesterasa , Butirilcolinesterasa , Humanos , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Simulación del Acoplamiento Molecular , Inhibidores de la Colinesterasa/farmacología , Relación Estructura-Actividad , Anhidrasa Carbónica I , alfa-Glucosidasas , Piridinas , Estructura Molecular
11.
J Biochem Mol Toxicol ; 36(4): e23001, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35225413

RESUMEN

Here, we report the synthesis, characterization, and biological activities of a series of benzimidazolium salts bearing the trifluoromethylbenzyl group. All benzimidazolium salts were characterized by using nuclear magnetic resonance (NMR) (1 H NMR and 13 C NMR), Fourier transform-infrared spectroscopy, and elemental analysis techniques. The crystal structures of some of these compounds were obtained by the single-crystal X-ray diffraction method. Furthermore, the acetylcholinesterase (AChE) and α-glycosidase (α-Gly) enzyme inhibition activities of these compounds were investigated. The obtained results revealed that 2e, with Ki value of 1.36 ± 0.34 µM against AChE and 3d with Ki value of 91.37 ± 10.38 µM against α-Gly, were the most potent compounds against both assigned enzymes. It should be noted that most of the synthesized compounds were more potent than standard inhibitor tacrine (TAC) against AChE. In silico studies, we focused on compound 2e, 3d, 3e, and 3f as potent inhibitors of AChE and α-Gly, the compound 2e showed good binding energy (-10.23 kcal/mol), among the three selected compounds and positive control (-10.18, -10.08, and -7.37 kcal/mol for 3d, 3f, and TAC, respectively). Likewise, as a result of the same compounds against the α-Gly enzyme, the compound 3d had the highest binding affinity (-8.39 kcal/mol) between the four selected compounds and the positive control (-8.27, -8.10, -8.06, and -7.53 kcal/mol for 3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug-likeness properties in the prediction studies compared to positive controls.


Asunto(s)
Acetilcolinesterasa , Sales (Química) , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de Glicósido Hidrolasas/química , Glicósido Hidrolasas/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Sales (Química)/química , Sales (Química)/farmacología , Relación Estructura-Actividad
12.
Exp Clin Transplant ; 20(6): 613-615, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-30836906

RESUMEN

Spleen abscess is a life-threatening disease. Treatment can be done by medical, radiological, or surgical methods. Here, we offer an innovative method of laparoscopic trocar-assisted percutaneous abscess drainage in the treatment of splenic abscess. Our patient, a 48-year-old male who had a kidney transplant 3 years previously, was admitted due to abdominal pain and fever. A-25-cm splenic abscess was detected, and ultrasonography-guided percu-taneous catheter 10F drainage was attempted. However, this attempt was not successful due to the high viscosity of the abscess content. Under general anesthesia, we then attempted abscess drainage percutaneously via a 12-mm laparoscopic trocar, and a large-bore drain of 28F was inserted into the abscess cavity. The drainage was successful (5300 mL high viscosity content) without any complications. The patient was discharged on day 8 and remained well at 9-month follow-up. Percutaneous drainage instead of splenectomy is preferred in the treatment of spleen abscess by preserving the immunologic functions of the spleen, particularly in immunocompromised patients. When percutaneous catheter drainage therapy fails, percutaneous treatment with a laparoscopic trocar is an innovative and reliable alternative.


Asunto(s)
Trasplante de Riñón , Laparoscopía , Enfermedades del Bazo , Absceso/diagnóstico por imagen , Absceso/cirugía , Drenaje/métodos , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Enfermedades del Bazo/diagnóstico por imagen , Enfermedades del Bazo/etiología , Enfermedades del Bazo/cirugía , Instrumentos Quirúrgicos , Resultado del Tratamiento
13.
Obes Res Clin Pract ; 15(3): 297-299, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33766490

RESUMEN

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed bariatric surgery in recent years, and some modifications have emerged to improve its efficacy. Melissas has described SG plus jejuno-ileal bypass (JIB), which has reported good results in a few studies. We performed this procedure in 21 cases and in one case, we observed acute liver failure (ALF) that has not been reported before. CASE PRESENTATION: A 38-year-old female (BMI: 56.1 kg/m2) underwent laparoscopic SG plus JIB. There was no sign of diarrhea, malnutrition or liver failure for eight months and her BMI was 43.0 kg/m2. At the 9th month, she was hospitalized for abdominal pain, jaundice and ALF. The patient was treated by plasmapheresis and molecular absorptive recirculation system. She was planned to undergo liver transplantation but died of multiorgan failure on the 40th day of hospitalization. CONCLUSION: ALF can be observed following SG plus JIB. JIB reversal before compromising liver functions should be taken into consideration.


Asunto(s)
Derivación Gástrica , Laparoscopía , Fallo Hepático Agudo , Obesidad Mórbida , Adulto , Femenino , Gastrectomía/efectos adversos , Humanos , Derivación Yeyunoileal , Laparoscopía/efectos adversos , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/cirugía , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
14.
Arch Pharm (Weinheim) ; 354(5): e2000422, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33427318

RESUMEN

Chloro-/fluorobenzyl-substituted benzimidazolium salts were synthesized from the reaction of 4-fluorobenzyl/2-chloro-4-fluorobenzyl-substituted benzimidazole and chlorinated aromatic hydrocarbons. They were characterized using various spectroscopic techniques (Fourier-transform infrared and nuclear magnetic resonance) and elemental analysis. In addition, the crystal structures of the complexes 1a -d and 2b were determined by single-crystal X-ray diffraction methods. These compounds were crystallized in the triclinic crystal system with a P-1 space group. The crystal packing of all complexes is dominated by O-H⋯Cl hydrogen bonds, which link the water molecules and chloride anions, forming a chloride-water tetrameric cluster. These synthesized salts were found to be effective inhibitors for α-glycosidase and acetylcholinesterase (AChE), with Ki values ranging from 45.77 ± 6.83 to 102.61 ± 11.56 µM for α-glycosidase and 0.94 ± 0.14 to 10.24 ± 1.58 µM for AChE. AChE converts acetylcholine into choline and acetic acid, thus causing the return of a cholinergic neuron to its resting state. Discovering AChE and α-glycosidase inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease and diabetes.


Asunto(s)
Bencimidazoles/farmacología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Acetilcolinesterasa/metabolismo , Bencimidazoles/síntesis química , Bencimidazoles/química , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Glicósido Hidrolasas/metabolismo , Humanos , Modelos Moleculares , Estructura Molecular , Sales (Química)/síntesis química , Sales (Química)/química , Sales (Química)/farmacología , Relación Estructura-Actividad
15.
Surg Infect (Larchmt) ; 22(7): 705-712, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33416442

RESUMEN

Background: It is a challenging question, especially in bariatric surgery (BS), whether antibiotic prophylaxis is necessary in all cases; considering the serious consequences of surgical site infection (SSI) on the one hand and irrational use of antibiotics on the other. The aim of this study was to determine the need/rationale for antibiotic prophylaxis in patients undergoing laparoscopic bariatric surgery, especially low-risk patients. Methods: This retrospective analysis involved 313 morbidly obese patients (body Mass Index [BMI] ≥40) who underwent laparoscopic BS at three medical centers between September 2018 and June 2019. During the trial, no inducement was given to use antibiotics, and the centers had chosen whether to use prophylaxis. The U.S. Centers for Disease Control and Prevention (CDC)-2016 criteria were used for the diagnosis of SSI. Results: Antibiotic prophylaxis was given to 181 patients, and the SSI rate in the entire series was 4.5% (14/313). There was no significant difference in SSI between the group who received antibiotics and that who did not (2.8% versus 6.8%, respectively; p = 0.09). Post-operative intra-abdominal complications were the main independent determinant for SSIs (p < 0.001). Antibiotic prophylaxis did not have any significant effect on the rate of SSI caused by these complications (2.2% versus 3.8%, respectively; p = 0.50). The second independent factor was the rate of SSI in patients with super-obesity (BMI ≥60), particularly incisional SSIs (p < 0.001). Antibiotic prophylaxis did not produce any significant decrease in the rate of SSI in patients with a BMI < 60 (2.8% versus 5.5%, respectively; p = 0.24). When these two independent factors were excluded, there were no patients with SSI in the no-antibiotics group, and only one in the antibiotic prophylaxis group (0.5%) (p = 1.00). Conclusions: Routine antibiotic prophylaxis should be questioned in laparoscopic BS. Prophylaxis may reduce incisional SSI in patients with a BMI of ≥60. In other cases, antibiotic prophylaxis does not provide a decrease in SSI.


Asunto(s)
Cirugía Bariátrica , Laparoscopía , Obesidad Mórbida , Profilaxis Antibiótica , Cirugía Bariátrica/efectos adversos , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control
16.
Int J Med Robot ; 16(6): 1-9, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32757483

RESUMEN

BACKGROUND: Data regarding the outcomes of pure minimally invasive techniques of radical gastrectomy are scarce. We aimed to compare short-term post-operative outcomes in patients undergoing totally minimally invasive radical gastrectomy with the da Vinci Xi® robotic system versus straight laparoscopy for gastric adenocarcinoma. METHODS: Between December 2013 and March 2018, robotic and laparoscopic radical gastrectomy performed in two centres were included. Both groups were compared with respect to perioperative short-term outcomes. RESULTS: Ninety-four patients were included in the study. Anticoagulant and neoadjuvant chemotherapy use were higher in the robotic group (p = 0.02, p = 0.02). There were conversions in the laparoscopy group whereas no conversions occurred in the robotic group (p = 0.052). Operating time in the robotic group was longer (p = 0.001). The number of harvested lymph nodes in the laparoscopic group was higher (p = 0.047). CONCLUSION: Totally robotic technique with the da Vinci Xi® robotic system provides similar short-term results compared to laparoscopic surgery in radical gastrectomy.


Asunto(s)
Adenocarcinoma , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Adenocarcinoma/cirugía , Gastrectomía , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
17.
Obes Surg ; 30(7): 2693-2699, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32279184

RESUMEN

OBJECTIVE: Bariatric surgery is not a risk-free procedure and requires lifelong patient compliance in the postoperative period. Although the risks involved in bariatric surgery and the importance of lifelong follow-ups in the postoperative period are explained to patients in detail through verbal and written informed consent, the strong desire for weight loss can sometimes cause patients and their families to be ignorant of the mentioned issues preoperatively. The objective of this study is to evaluate the effectiveness of preoperative informational videos at improving the comprehension of informed consent content in bariatric surgery candidates. MATERIALS AND METHODS: A total of 74 bariatric surgery candidates were randomized into two groups. The first group was given a usual verbal-written informed consent. The second group got an additional informing video presentation informed consent, in addition to the usual verbal-written informed consent. Then, both groups got a questionnaire evaluating their knowledge of bariatric surgery informed consent. The correct response scores and their relationship with patient demographics were analyzed. RESULTS: Both groups had similar demographic features. Video-presented group had higher scores in questionnaire (11.3 ± 2.3 versus 9.4 ± 1.7, p = 0.001). Subgroup analysis showed that health care workers (12.5 ± 1.9 versus 10.3 ± 2.2, p = 0.005) and university graduates (11.6 ± 2.4 versus 10.1 ± 2.1, p = 0.03) got better results in the questionnaire. In multivariate analysis, video-assisted informing was found to be the only independent variable for high questionnaire scores (p = 0.0001). CONCLUSIONS: This study showed that video-assisted informed consent improves patients' comprehension prior to bariatric surgery. We recommend routine preoperative video-assisted informing for bariatric surgery candidates in addition to usual verbal-written informed consent.


Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida , Comprensión , Humanos , Consentimiento Informado , Obesidad Mórbida/cirugía , Encuestas y Cuestionarios
18.
Bioorg Chem ; 95: 103552, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31911299

RESUMEN

In recent years, the preparation of metal complexes and the introduction of biologically active organometalic compounds are new strategies in drug development. For this purpose, generally N-heterocyclic pharmaceutical agents have been used as promising nuclei. Au-containing N-heterocyclic carbene (Au-NHC) derivatives are among the compounds used for this purpose, and their enzyme inhibition, antioxidant activity, antimicrobial and anticancer properties are widely studied. In these studies, the anticancer property of Au-NHC complexes is the most widely studied area. The common result in different studies has been revealed that mitochondrial thioredoxin reductases (TrxR) inhibition is the main pathway in the powerful anticancer effect of many Au-NHC complexes. In TrxR inhibition, the high affinity of gold to sulfur is considered to be the main component of the effect. This review includes the discussions releated to the anticancer activities and TrxR inhibition properties of Au-NHC compounds.


Asunto(s)
Antineoplásicos/farmacología , Oro/química , Compuestos Heterocíclicos/farmacología , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Antineoplásicos/química , Línea Celular Tumoral , Compuestos Heterocíclicos/química , Humanos
19.
Turk J Surg ; 36(4): 333-339, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33778391

RESUMEN

OBJECTIVES: The most common intra-abdominal complication following loop ileostomy closure (LIC) is postoperative ileus (POI). The aim of the study was to determine the risk factors of POI development following LIC and make recommendations for its prevention. MATERIAL AND METHODS: In this study, patients having undergone LIC with peristomal incision following distal colorectal surgery were included. Clavien-Dindo classification was used to evaluate postoperative complications. POI and postoperative leakage were defined based on clinical and radiological criteria. The Centers for Disease Control and Prevention 2017 criteria were used to diagnose surgical site infection (SSI). Postoperative bleeding was diagnosed one day after surgery if there was a >2 g/dL or ≥15% decrease in the hemoglobin level. RESULTS: Seventy-nine patients were included into the study. In nine of the patients POI developed, six had SSI, five had postoperative bleeding, and two had anastomosis leakage. In the univariate analysis; age <60 years (p= 0.02), presence of comorbidity (p= 0.007), using an open technique in the first surgery (p= 0.02), performing total colectomy in the first surgery (p= 0.048), performing hand-sewn anastomosis of LIC (p= 0.01), and postoperative blood transfusion (p= 0.04) were found to be risk factors for POI. Performing hand-sewn anastomosis of LIC (p= 0.03) and using an open technique in the first surgery (p= 0.03) were found to be independent variables for POI risk. CONCLUSION: Using an open technique in the first surgery and performing a hand-sewn anastomosis of LIC may increase POI.

20.
Bioorg Chem ; 94: 103468, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31791684

RESUMEN

In this work, structures of different imidazolium compounds were designed and synthesized. These compounds were synthesized from 2-methylimidazole and alkyl/aryl halides. Their structures were characterized by using 1H NMR, 13C NMR, FTIR spectroscopic techniques. All the synthesized compounds were tested for their inhibition activities on different enzymes. Inhibition experiments gave good and moderate results, proving their activities of these compounds as anticholinergics potential. These obtained novel 2-methylimidazolium salts (1a-e and 2a-e) molecules were effective inhibitors of the carbonic anhydrase I and II isozymes (hCA I and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 26.45 ± 6.49-77.60 ± 9.53 nM for hCA I, 27.87 ± 5.00-86.61 ± 5.71 nM for hCA II, and 1.15 ± 0.19-8.89 ± 0.49 nM for AChE, respectively. AChE enzyme inhibitors are the most common drugs applied in the therapy of diseases such as senile dementia, Alzheimer's disease, ataxia, Parkinson's disease, and among others.


Asunto(s)
Acetilcolinesterasa/metabolismo , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica I/antagonistas & inhibidores , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de la Colinesterasa/farmacología , Imidazoles/farmacología , Anhidrasa Carbónica I/metabolismo , Anhidrasa Carbónica II/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Relación Dosis-Respuesta a Droga , Humanos , Imidazoles/síntesis química , Imidazoles/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Sales (Química)/síntesis química , Sales (Química)/química , Sales (Química)/farmacología , Relación Estructura-Actividad
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