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Bazı Yeni 2-Pirazolin Türevlerinin Sentezi ve Monoamin Oksidaz (Mao) İnhibitör Aktiviteleri Üzerinde Çalışmalar

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10073184 Umut SALGIN GÖKŞEN doktora tez.pdf (11.34Mb)
Date
2015
Author
Salgın Gökşen, Umut
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Abstract
In this study, forty two compounds which have 1-[2-(5-substituted-2- benzoxazolinone-3-yl)acetyl]-3,5-disubstitutedphenyl-4,5-dihydro-1H-pyrazole structure and nine compounds which have N’-(1,3-disubstitutedphenylallylidene)-2- (5-substituted-2-benzoxazolinone-3-yl)acetohydrazide structure have been synthesized, structures of the compounds have been proved by spectral techniques, their purity have been checked by elemental analyses and their interactions with MAO-A/MAO-B isoforms have been investigted by molecular docking. MAO inhibitory activities and selectivities of the compounds have been determined by in vitro tests using human MAO-A and -B isoforms. Compound 6 has been seperated to its enantiomers by analytical high pressure liquid chromatograpy (HPLC), fractions have been collected by semipreparative HPLC, the spesific rotations have been found and the absolute configurations have been determined by vibrational circular dichroism (VCD) technique. It was found that R isomer is more active than S isomer in terms of MAO-A inhibition. Following that, acute and subchronic antidepressant effects of five compounds have been evaluated via Porsolt’s forced swimming test (PFST) on mice. After the in vivo tests, brain tissues of the mice were isolated and level of the serotonine, dopamine (DA) and their metabolites were determined in brain tissues. Contrary to expectations, compounds increased the DA level. It was thought that, this was result from the screening dose (30 mg/kg) was relatively high and for this reason dose-response studies were done to determine the efficient selective dose. Additionally, open field test was done to assess whether the increase on DA level has effected the locomotor activities of mice and PFST results indirectly.
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http://hdl.handle.net/11655/1132
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  • Eczacılık Meslek Bilimleri Bölümü Tez Koleksiyonu [94]
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