Yeni bazı flavonoid türevlerinin sentezi, kimyasal yapılarının aydınlatılması ve monoamin oksidaz enzimleri üzerine etkilerinin araştırılması
Investigations on synthesis, chemical structure elucidation and effects on monoamine oxidase enzyme of some new flavonoid compounds
Yazar: BEGÜM EVRANOS
Danışman: PROF. DR. RAHMİYE ERTAN
Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı
Derece: Doktora, 2010
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology
Dizin: Enzimler = Enzymes ; Flavonoidler = Flavonoids ; Hidrazonlar = Hydrazones ; Kalkonlar = Chalcones ; Monoamin oksidaz = Monoamine oxidases ; Monoamin oksidaz inhibitörleri = Monoamine oxidases inhibitors ; Pirazolinler = Pyrazolines

Özet:
Bu çalışmada, asetofenon (Ia-j) ve benzaldehit (IIa-d) türevlerinin metanol içinde KOH varlığında reaksiyonu ile şalkon türevleri (IIIa-u) elde edilmiş, elde edilen şalkonların etanol içinde hidrazit türevleriyle (IVa-f) ısıtılmasıyla hidrazon (Va-s) ve 2-pirazolin (VIa-u) yapısında bazı yeni moleküllerin sentezleri gerçekleştirilmiştir. Böylece şalkon (2), hidrazon (18) ve 2-pirazolin (20) türevleri olan toplam 40 orijinal kimyasal madde elde edilmiş ve bunların yapı tayinlerinde Elementel Analiz, IR, 1H-NMR ve Mass spektral yöntemlerinden yararlanılmıştır. Sentezlenen bileşiklerin, MAO enzimi üzerindeki inhibisyon yapıcı etkileri incelenmiş ve sonuçta VIa, VIc, VIf ve VIl bileşiklerinin referans bileşik moklobemide yakın düzeyde MAO-A enzimi üzerinde inhibisyon yapıcı etki gösterdikleri saptanmıştır. Sentezlenen orijinal bileşiklerin kimyasal okunuşları aşağıda bir arada verilmiştir;IIIc (E)-1-(3,5-dikloro-2-hidroksifenil)-3-m-tolilprop-2-en-1-onIIIo (E)-1-(4-bromofenil)-3-m-tolilprop-2-en-1-onVa (E)-N'-((E)-1-(2,4-dimetoksifenil)-3-p-tolilalliliden)tiyofen-2-karbohidrazidVb(E)-N'-((E)-1-(2,4-dimetoksifenil)-3-p-tolilalliliden)furan-2-karbohidrazidVc (E)-N'-((E)-1-(4-florofenil)-3-(4-metoksifenil)alliliden)tiyofen-2-karbohidrazidVd (E)-N'-((E)-1-(4-florofenil)-3-(4-metoksifenil)alliliden)-4-metil-1,2,3-tiyadiazol-5- karbohidrazidVe (E)-N'-((E)-1-(4-florofenil)-3-p-tolilalliliden)tiyofen-2-karbohidrazidVf (E)-N'-((E)-1-(4-florofenil)-3-m-tolilalliliden)tiyofen-2-karbohidrazidVg (E)-N'-((E)-1-(4-bromofenil)-3-p-tolilalliliden)tiyofen-2-karbohidrazidVh (E)-N'-((E)-1-(4-bromofenil)-3-p-tolilalliliden)-4-metil-1,2,3-tiyadiazol-5-karbohidrazidVi (E)-N'-((E)-1-(4-bromofenil)-3-(4-metoksifenil)alliliden)-4-metoksibenzohidrazidVj (E)-N'-((E)-1-(4-bromofenil)-3-m-tolilalliliden)-4-metil-1,2,3-tiyadiazol-5-karbohidrazidVk (E)-N'-((E)-1-(4-bromofenil)-3-(4-metoksifenil)alliliden)furan-2-karbohidrazidVl (E)-N'-((E)-1-(4-klorofenil)-3-p-tolilalliliden)tiyofen-2-karbohidrazidVm (E)-N'-((E)-1-(4-klorofenil)-3-p-tolilalliliden)-4-metil-1,2,3-tiyadiazole-5-karbohidrazidVn (E)-N'-((E)-1-(4-klorofenil)-3-m-tolilalliliden)-4-metil-1,2,3-tiyadiazole-5-karbohidrazidVo(E)-N'-((E)-1-(4-klorofenil)-3-(4-metoksifenil)alliliden)-4-metil-1,2,3-tiyadiazol-5-karbohidrazidVp (E)-N'-((E)-1-(4-klorofenil)-3-(4-metoksifenil)alliliden)-4-metoksibenzohidrazidVr (E)-N'-((E)-1-(4-hidroksifenil)-3-p-tolilalliliden)-4-metil-1,2,3-tiyadiazol-5- karbohidrazidVs (E)-N'-((E)-1-(4-metoksifenil)-3-p-tolilalliliden)-4-metil-1,2,3-tiyadiazol-5-karbohidrazidVIa(3-(5-kloro-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(piridin-4-il) metanonVIb (3-(5-kloro-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(furan-2- il)metanonVIc (3-(5-kloro-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(fenil) metanonVId (3-(5-kloro-2-hidroksifenill)-5-p-tolil-4,5-dihidropirazol-1-il)(4-metoksifenil) metanonVIe (3-(5-kloro-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(4-metil-1,2,3-tiyadiazol-5-il)metanonVIf (3-(3,5-dikloro-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(4-metoksifenil) metanonVIg (3-(3,5-dikloro-2-hidroksifenil)-5-m-tolil-4,5-dihidropirazol-1-il)(piridin-4-il) metanonVIh (3-(3,5-dikloro-2-hidroksifenil)-5-m-tolil-4,5-dihidropirazol-1-il)(furan-2-il) metanonVIi (3-(3,5-dikloro-2-hidroksifenil)-5-m-tolil-4,5-dihidropirazol-1-il)(fenil) metanonVIj (3-(3,5-dikloro-2-hidroksifenil)-5-m-tolil-4,5-dihidropirazol-1-il)(4-metoksifenil) metanonVIk (3-(3,5-dikloro-2-hidroksifenil)-5-m-tolil-4,5-dihidropirazol-1-il)(4-metil-1,2,3-tiyadiazol-5-il)metanonVIl (3-(5-bromo-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(piridin-4-il)metanonVIm (3-(5-bromo-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(furan-2-il) metanonVIn (3-(5-bromo-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(fenil)metanonVIo (3-(5-bromo-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(4-metoksifenil) metanonVIp (3-(5-Bromo-2-hidroksifenil)-5-p-tolil-4,5-dihidropirazol-1-il)(tiyofen-2-il) metanonVIr (3-(2-hidroksi-4-metoksifenil)-5-(2-metoksifenil)-4,5-dihidropirazol-1-il)(fenil) metanonVIs (3-(2-hidroksi-4-metoksifenil)-5-(4-metoksifenil)-4,5-dihidropirazol-1-il)(4-metoksifenil)metanonVIt (3-(5-bromo-2-hidroksifenil)-5-(4-metoksifenil)-4,5-dihidropirazol-1-il)(4-metoksifenil)metanonVIu (3-(5-kloro-2-hidroksifenil)-5-(4-metoksifenil)-4,5-dihidropirazol-1-il)(tiyofen-2-il) metanonAnahtar kelimeler: Docking, Hidrazon, MAO enzim inhibisyonu, 2-Pirazolin, Sentez ve yapı aydınlatma, Şalkon (prop-2-en-1-on) türevleri

Abstract:
In this study, chalcone derivatives (IIIa-u) were prepared with the reaction of some acetophenone (Ia-j) and benzaldehyde derivatives (IIa-d) in KOH/MeOH. The ensuing chalcone derivatives (IIIa-u) are then reacted with some hydrazide compounds to furnish hydrazone (Va-s) and 2-pyrazoline (VIa-u) derivatives. The structure of synthesized original chalcone (2), hydrazone (18) and 2-pyrazoline (20) derivatives was elucidated by IR, 1H NMR, Mass spectral data and elementary analysis findings. The synthesized compounds were tested for their MAO inhibitor activities and it is found that compounds VIa, VIc, VIf and VIl have similar activities as moclobemide. Chemical names of synthesized compounds are given below;IIIc (E)-1-(3,5-Dichloro-2-hydroxyphenyl)-3-m-tolylprop-2-en-1-oneIIIo (E)-1-(4-Bromophenyl)-3-m-tolylprop-2-en-1-onVa (E)-N'-((E)-1-(2,4-Dimethoxyphenyl)-3-p-tolylallylidene)thiophene-2-carbohydrazideVb (E)-N'-((E)-1-(2,4-Dimethoxyphenyl)-3-p-tolylallylidene)furan-2-carbohydrazideVc (E)-N'-((E)-1-(4-Fluorophenyl)-3-(4-methoxyphenyl)allylidene)thiophene-2-carbohydrazideVd (E)-N'-((E)-1-(4-Fluorophenyl)-3-(4-methoxyphenyl)allylidene)-4-methyl-1,2,3-thiadiazole-5-carbohydrazideVe (E)-N'-((E)-1-(4-Fluorophenyl)-3-p-tolylallylidene)thiophene-2-carbohydrazideVf (E)-N'-((E)-1-(4-Fluorophenyl)-3-m-tolylallylidene)thiophene-2-carbohydrazideVg (E)-N'-((E)-1-(4-Bromophenyl)-3-p-tolylallylidene)thiophene-2-carbohydrazideVh (E)-N'-((E)-1-(4-Bromophenyl)-3-p- tolylallylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVi (E)-N'-((E)-1-(4-Bromophenyl)-3-(4-methoxyphenyl)allylidene)-4-methoxy benzohydrazideVj (E)-N'-((E)-1-(4-Bromophenyl)-3-m-tolylallylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVk (E)-N'-((E)-1-(4-Bromophenyl)-3-(4-methoxyphenyl)allylidene)furan-2-carbohydrazideVl (E)-N'-((E)-1-(4-Chlorophenyl)-3-p-tolylallylidene)thiophene-2-carbohydrazideVm (E)-N'-((E)-1-(4-Chlorophenyl)-3-p-tolylallylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVn (E)-N'-((E)-1-(4-Chlorophenyl)-3-m-tolylallylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVo (E)-N'-((E)-1-(4-Chlorophenyl)-3-(4-metoxyphenyl)allylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVp (E)-N'-((E)-1-(4-Chlorophenyl)-3-(4-metoxypheny)allylidene)-4-metoxybenzohidrazideVr (E)-N'-((E)-1-(4-Hydroxyphenyl)-3-p-tolylallylidene)-4-methyl-1,2,3-thiadiazole-5- carbohidrazideVs (E)-N'-((E)-1-(4-Metoxyphenyl)-3-p-tolylallylidene)-4-methyl-1,2,3-thiadiazole-5-carbohidrazideVIa(3-(5-Chloro-2-hidroxyphenyl)-5-p-tolyl-4,5-dihydropyrazole-1-yl)(pyridine-4-yl) methanoneVIb (3-(5-Chloro-2-hidroxyphenyl)-5-p-tolyl-4,5-dihydropyrazole-1-yl)(furan-2- yl)methanoneVIc (3-(5-Chloro-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazole-1-yl)(phenyl) methanoneVId (3-(5-Chloro-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazole-1-yl)(4-metoxyphenyl) methanoneVIe (3-(5-Chloro-2-hydroxyphenyl)-5-p-tolyl-4,5-dihidropyrazole-1-yl)(4-methyl-1,2,3-thiadiazole-5-yl)methanoneVIf (3-(3,5-Dichloro-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazole-1-yl)(4-metoxyphenyl) methanoneVIg (3-(3,5-Dichloro-2-hydroxyphenyl)-5-m-tolyl-4,5-dihidropyrazole-1-il)(pyridine-4-il) metanoneVIh (3-(3,5-Dichloro-2-hydroxyphenyl)-5-m-tolyl-4,5-dihidropyrazole-1-yl)(furan-2-yl) methanoneVIi (3-(3,5-Dichloro-2-hydroxyphenyl)-5-m-tolyl-4,5-dihydropyrazole-1-yl)(phenyl) methanoneVIj (3-(3,5-Dichloro-2-hydroxyphenyl)-5-m-tolyl-4,5-dihydropyrazole-1-yl)(4-metoxyphenyl) methanoneVIk (3-(3,5-Dichloro-2-hydroxyphenyl)-5-m-tolyl-4,5-dihydropyrazole-1-yl)(4-methyl-1,2,3-thiadiazole-5-yl)methanoneVIl (3-(5-Bromo-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(pyridine-4-yl)methanoneVIm (3-(5-Bromo-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(furan-2-yl) methanoneVIn (3-(5-Bromo-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl)methanoneVIo (3-(5-Bromo-2-hydroxyphenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(4-metoxyphenyl) methanoneVIp (3-(5-Bromo-2-hydroxypheny)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(thiophene-2-yl) methanoneVIr (3-(2-Hydroxy-4-metoxyphenyl)-5-(2-metoxyphenyl)-4,5-dihydropyrazol-1-yl)(phenyl) methanoneVIs (3-(2-Hydroxy-4-metoxyphenyl)-5-(4-metoxyphenyl)-4,5-dihydropyrazol-1-yl)(4-metoxyphenyl)methanoneVIt (3-(5-Bromo-2-hydroxyphenyl)-5-(4-metoxyphenyl)-4,5-dihydropyrazol-1-yl)(4-metoxyphenyl)methanoneVIu (3-(5-Chloro-2-hydroxyphenyl)-5-(4-metoxyphenyl)-4,5-dihydropyrazol-1-yl)(thiophen-2-yl) methanoneKeywords: Chalcone (prop-2-en-1-one) derivatives, Docking, Hydrazone, MAO enzyme inhibition, 2-Pyrazoline, Synthesis and structure elucidation