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Tromsø, Norway

Samshuddin S.,Mangalore University | Narayana B.,Mangalore University | Sarojini B.K.,P.A. College | Khan M.T.H.,Holmboevegen 3B | And 3 more authors.
Medicinal Chemistry Research | Year: 2012

A series of 1,3,5-triaryl-2-pyrazolines 2a-g were synthesized by the reaction of 4,40-disubstituted chalcone with phenyl hydrazine. All these compounds were characterized by NMR, IR and mass spectral and single crystal XRD data. All the synthesized products were screened for their in vitro antimicrobial, analgesic and antioxidant properties. The docking studies were carried out for these compounds against the active site of methionyl-tRNA synthetase (metRS). Some of the tested compounds exhibited significant antimicrobial, analgesic, DPPH scavenging activities and molecular binding. © Springer Science+Business Media, LLC 2011. Source


Murakawa T.,Toyohashi University of Technology | Matsushita Y.,Toyohashi University of Technology | Suzuki T.,Toyohashi University of Technology | Khan M.T.H.,Holmboevegen 3B | Kurita N.,Toyohashi University of Technology
Journal of Molecular Graphics and Modelling | Year: 2014

Butyrylcholinesterase (BChE) exists mainly at neuromuscular junctions and plays an important role in the hydrolyzing mechanism of neurotransmitter acetylcholine. A variety of compounds have been produced in order to inhibit the function of BChE. We here investigate the specific interactions between BChE and some ligands (Kx) with large binding affinity to BChE, using ligand-docking, classical molecular mechanics and ab initio fragment molecular orbital (FMO) methods. The binding energies between BChE and Kx evaluated by the FMO method have a correlation with the 50% inhibition concentration obtained by the previous experiments. In addition, the FMO calculations highlight that Asp70, Trp82 and Tyr128 residues of BChE contribute significantly to the binding between BChE and Kx. Based on the results, we propose some novel ligands and elucidate that one of the proposed ligands can bind strongly to BChE. The present results are useful for developing potent inhibitors to BChE. © 2014 Elsevier Inc. All rights reserved. Source


Senol F.S.,Gazi University | Skalicka Wozniak K.,Medical University of Lublin | Khan M.T.H.,Holmboevegen 3B | Erdogan Orhan I.,Gazi University | And 3 more authors.
Phytochemistry Letters | Year: 2011

Cholinesterase inhibitory and antioxidant activities of the methanol extract, furanocoumarin fraction, and major coumarins (imperatorin, xanthotoxin, and bergapten) of the fruits of Angelica officinalis L. growing in Poland were determined in the current study. Cholinesterase inhibition was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 12.5, 25, 50, and 100 μg mL-1 using ELISA microplate reader. Antioxidant activity of the samples was tested by in vitro models including radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), N,N-dimethyl-p-phenylendiamine (DMPD) as well as ferrous ion-chelation capacity, ferric-(FRAP) and phosphomolibdenum-reducing antioxidant power (PRAP) assays at 500, 1000, and 2000 μg mL-1. The extract was found to have strong inhibition against BChE (85.65 ± 1.49%) and low inhibition against AChE (27.49 ± 2.01%) at 100 μg mL-1. Four major coumarins; imperatorin, isoimperatorin, xanthotoxin, and bergapten were identified in the extract by HPLC. Imperatorin (83.98 ± 0.99%), xanthotoxin (88.04 ± 0.83%), and bergapten (86.69 ± 2.56%) displayed strong inhibition towards BChE. Molecular docking studies confirmed potent interactions between BChE and the tested furanocoumarins. The samples did not possess radical scavenging activity against DPPH and DMPD, whereas they possessed a moderate level of FRAP and PRAP at the tested concentrations. To the best of our knowledge, the current work constitutes the first study on cholinesterase inhibitory and antioxidant activities of A. officinalis. © 2011 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved. Source


Kovarova M.,University of Pardubice | Khan M.T.H.,Holmboevegen 3B | Komers K.,University of Pardubice | Parik P.,University of Pardubice | And 2 more authors.
Current Enzyme Inhibition | Year: 2011

Two series A and B of 12 and 7 new carbamate derivates were tested in vitro as acetylcholinesterase inhibitors. The tests were performed in the batch stirred reactor at 25°C, pH 8, ionic strength 0.11 M and catalytic activity of the enzyme preparation 0.14 U mL -1 of the reaction mixture. The temporal dependences of actual concentrations of acetylcholine, choline and acetic acid were determined by two independent analytical methods, HPLC and pH-stat. For all used inhibitors, the model of competitive irreversible inhibition was valid. The inhibition rate constant k 3 and qualified estimation of the absolute acetylcholinesterase concentration in the reaction mixture were calculated. The partition coefficients K ow between n-octanol and water of all used inhibitors were determined. The k 3 and K ow values were correlated with the Hammett and Hansch substituent constants and with the calculated docking and binding energies of the reaction between the tested inhibitors and acetylcholinesterase. © 2011 Bentham Science Publishers. Source


Senol F.S.,Gazi University | Khan M.T.H.,Holmboevegen 3B | Orhan G.,Numune Training and Research Hospital | Gurkas E.,Numune Training and Research Hospital | And 3 more authors.
Current Topics in Medicinal Chemistry | Year: 2014

Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase or some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated by three histidines is a bifunctional enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson's disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin 283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41 Å, respectively, through its O5 atom. © 2014 Bentham Science Publishers. Source

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