Browsing by Author "Yabanoğlu-Çiftçi, Samiye"

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Citation Count: 123
New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis biological evaluation and structural determinants of MAO-A and MAO-B selectivity
(Pergamon-Elsevier Science Ltd, 2009) Yelekçi, Kemal; Koyunoğlu, Semra; Yabanoğlu-Çiftçi, Samiye; Yelekçi, Kemal; Özgen, Özen; Uçar, Gülberk; Erol, Kevser; Kendi, Engin; Yeşilada, Akguel; Yelekçi, Kemal
A new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h 4j-4n and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Compounds 4i 4k 5e 5i and 5l were chosen for their ability to reversibly inhibit MAO-B and MAO-A and the availability of experimental inhibition data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Among the pyrazoline derivatives it appears that the binding interactions for this class of compounds are mostly hydrophobic. All have potential edge-to-face hydrophobic interactions with F343 as well as pi-pi stacking with Y398 and other hydrophobic interactions with L171. Strong hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the reason why this compound shows selectivity toward the MAO-B isoform. The very high MAO-B selectivity for 4i can be also explained in terms of the distance between the FAD and the compound which was greater in the complex of MAO-A-4i as compared to the corresponding MAO-B complex. (C) 2008 Elsevier Ltd. All rights reserved.
Citation Count: 20
Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2-Pyrazoline and Hydrazone Derivatives
(Wiley-VCH Verlag GmbH, 2015) Yelekçi, Kemal; Baysal, İpek; Yabanoğlu-Çiftçi, Samiye; Djikic, Teodora; Yelekçi, Kemal; Uçar, Gülberk; Ertan, Rahmiye
A group of 35-diaryl-2-pyrazoline and hydrazone derivatives was prepared via the reaction of various chalcones with hydrazide compounds in ethanol. Twenty original compounds were synthesized. Ten of these original compounds have a pyrazoline structure nine of these original compounds have a hydrazone structure and one of these original compounds has a chalcone structure. Structural elucidation of the compounds was performed by IR H-1 NMR C-13 NMR mass spectral data and elemental analyses. These compounds were tested for their inhibitory activities toward the A and B isoforms of human monoamine oxidase (MAO). Except for 3k and 6c all compounds were found to be competitive reversible and selective inhibitors for either one of the isoforms (hMAO-A or MAO-B). Compounds 3k and 6c were found to be competitive reversible but non-selective MAO inhibitors. Compound 6h showed hMAO-B inhibitory activity whereas the others potently inhibited hMAO-A. Compound 5c showed higher selectivity than the standard drug moclobemide. According to the experimental K-i values compounds 6i 6d and 6a exhibited the highest inhibitory activity toward hMAO-A. The AutoDock 4.2 program was employed to perform automated molecular docking. The calculated results obtained computationally were in good agreement with the experimental values.