MAO enzymes inhibitory activity of new benzimidazole derivatives including hydrazone and propargyl side chains

Can, Özgür Devrim; Osmaniye, Derya; Özkay, Ümide Demir; Sağlık, Begüm Nurpelin; Levent, Serkan; Ilgın, Sinem; Baysal, Merve; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1016/j.ejmech.2017.03.009

Cited by 69 publications

(60 citation statements)

References 47 publications

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“…Similarly, interactions of aromatic protons H h with C h carbon at 129.8 ppm, H i with C i carbon at 115 ppm, H e with C e carbon at 130.5 ppm, H f proton with C f carbon at 120.4 ppm were found. In the literature, it was reported that carbonyl peaks were observed at 160–180 ppm, so the peak at 160.79 ppm was accepted as carbonyl peak of oxazolidinone . As a result, the peaks at 131.72, 132.57, 136.81, 159.00 ppm belonged to the ipso carbons.…”

Section: Resultsmentioning

confidence: 99%

“…The compounds were tested between 3.9 and 500 μg/mL concentrations (500, 250, 125, 62.5, 31.25, 15.62, 7.8, and 3.9 μg/mL). Inhibition % was calculated for each concentration according to the formula below and IC 50 values were determined by plotting a dose–response curve of inhibition % versus compound concentrations tested

% I n h i b i t i o n = 100 - true(normalm normale normala normaln normals normala normalm normalp normall normale \times 100 / normalm normale normala normaln normals normalo normall normalv normale normaln normalt true)

…”

Section: Methodsmentioning

confidence: 99%

“…The genotoxicity of the most effective compounds was determined by Ames assay using Ames MPF 98/100 mutagenicity assay sample kit (Xenometrix AG, Switzerland) as previously described . Salmonella typhimurium strains, TA98 (frameshift mutations) and TA100 (base‐pair substitutions), are used in this assay.…”

Section: Methodsmentioning

confidence: 99%

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Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

Karaman

Zainel

Kapkac

et al. 2018

Archiv der Pharmazie

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1,3-Oxazolidine-2-one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1-22) were obtained by the reaction of (S)-4-(4-aminobenzyl)-2(1H)-1,3-oxazolidinone with 4-substituted benzoyl chlorides, 4-substituted benzene sulfonyl chlorides, and 4-substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT-IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram-positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non-mutagenic and non-cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16.

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Section: Resultsmentioning

confidence: 99%

% I n h i b i t i o n = 100 - true(normalm normale normala normaln normals normala normalm normalp normall normale \times 100 / normalm normale normala normaln normals normalo normall normalv normale normaln normalt true)

…”

Section: Methodsmentioning

confidence: 99%

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Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

Karaman

Zainel

Kapkac

et al. 2018

Archiv der Pharmazie

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“…Km and Vmax values belonging to inhibitor and control were calculated using junction points on the x-and y-axis. The slopes of the Lineweaver-Burk plots were replotted versus the inhibitor concentration and inhibitory constant (Ki) was calculated 30,31 . In the substrate level determination studies, tyramine quantity in blank well was regarded as 100% and substrate percent of compound including wells were calculated as mean ± SD.…”

Section: Discussionmentioning

confidence: 99%

Investigation of monoamine oxidase inhibitory activities of new chalcone derivatives

Can¹

2018

Cukurova Medical Journal

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In the present study, it is aimed to investigate monoamine oxidase (MAO) enzyme inhibition potencies of some new chalcone derivatives. Materials and Methods: Nine novel chalcone derivatives were synthesized and structures of the synthesized compounds (2a-2i) were confirmed by spectroscopic methods. Inhibitory activities of the compounds against MAO-A and MAO-B enzymes have been determined via in-vitro fluorometric method. Effects of the compounds on substrate level were measured by an LC-MS/MS method. Enzyme kinetics studies were carried out for the most active compound 2i using Lineweaver-Burk plots. Results: Compounds 2c, 2e and 2i displayed notable inhibition against hMAO-B with lower IC50 values than 1 µM. The most active compound 2i displayed significant inhibition by IC50 of 0.13 µM. Results of substrate level quantification study were in an agreement with fluorometric enzyme inhibition assay. Competitive type of inhibition was determined for compound 2i as a result of enzyme kinetic studies. Conclusion: Synthesized compounds displayed more selectivity towards hMAO-B. In this study, the results of inhibitor effects of compounds 2c, 2f and 2i are promising for the synthesis of similar derivatives with enhanced MAO inhibitory activity and therefore for the development of new molecules which may be drug candidates against Parkinson's disease.

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“…Enzymatic testing was conducted using the current fluorometric approach declared by our research community [ 14 , 15 , 16 , 17 , 18 ]. Sigma-Aldrich (Steinheim, Germany) provided the chemicals and reagents used in the test (AmplifluTM Red (10-Acetyl-3,7-dihydroxyphenoxazine), MAO-A, MAO-B, peroxidase from horseradish, tyramine hydrochloride, H 2 O 2 , moclobemide, clorgiline and selegiline) and they were maintained by the manufacturer under the specified conditions.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

et al. 2020

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Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as 1H-NMR, 13C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds 3c, 3d and 3e displayed significant MAO-A inhibition potencies. Among them, compound 3e was found to be the most effective derivative with an IC50 value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC50 = 6.061 ± 0.262 µM) and clorgiline (IC50 = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound 3e and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.

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MAO enzymes inhibitory activity of new benzimidazole derivatives including hydrazone and propargyl side chains

Cited by 69 publications

References 47 publications

Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

Investigation of monoamine oxidase inhibitory activities of new chalcone derivatives

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

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