Yeni biyolojik aktif hidrazon bileşiklerinin sentezi, aktivite çalışmaları ve in silico hesaplamalar
Synthesis of new biologically active hydrazone compounds, activity studies and in silico computations
Yazar: ELİF AYLİN AKYILDIZ
Danışman: PROF. DR. NURAY GÜZELDEMİRCİ ; DOÇ. DR. BERİN KARAMAN MAYACK
İstanbul Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı / Farmasötik Kimya Bilim Dalı
Derece: Yüksek Lisans, 2024
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology ; Kimya = Chemistry

Özet:
Bu tez çalışmasında 2,5-diklorobenzohidrazid bileşiğinden hareketle 15 adet yeni bileşik; 2,5-dikloro-N'-[(2-florofenil)metiliden]benzohidrazid (3a), N'-[(2-bromo fenil)metiliden]-2,5-diklorobenzohidrazid (3b), N'-[(4-bromofenil)metiliden]-2,5-diklorobenzohidrazid (3c), 2,5-dikloro-N'-[(4-klorofenil)metiliden]-benzohidrazid (3d), 2,5-dikloro-N'-[(4-siyanofenil)metiliden]-benzohidrazid (3e), 2,5-dikloro-N'-(4-hidroksibenziliden)benzohidrazid (3f), 2,5-dikloro-N'-{[4-(metilsülfanil)fenil]metiliden}- benzohidrazid (3g), 2,5-dikloro-N'-[(4-nitrofenil)metiliden]benzohidrazid (3h), 2,5-dikloro-N'-[(5-kloro-2-hidroksifenil(metiliden)]benzohidrazid (3i), 2,5-dikloro-N'-[(2,6-diklorofenil)metiliden]benzohidrazid (3j), 2,5-dikloro-N'-[(2,5-dimetoksifenil)metiliden]benzohidrazid (3k), N'-[(2H-1,3-benzodioksol-5-il)metiliden]-2,5-diklorobenzohidrazid (3l), 2,5-dikloro-N'-[(tiyofen-2-il)metilen)]benzohidrazid (3m), N'-[(5-bromo-1H-indol-3-il)metiliden]-2,5-diklorobenzohidrazid (3n), 2,5-dikloro-N'-{3-[4-(dimetilamino)fenil]prop-2-en-1-iliden}benzohidrazid (3o) sentezlendi. Bileşiklerin yapı tayinleri elementel analiz ve spektroskopik yöntemler (UV, IR, NMR (1H-NMR,13C-NMR (APT), HSQC), ESI-MS) kullanılarak elde edilen veriler ile doğrulandı. Ayrıca bileşiklerin in silico çalışmaları ile ADME, toksikolojik özellikleriyle, metabolizmal Faz I ile Faz II metabolitlerinin tespit edilmesinde çevrimiçi programlar (Shrödinger, XUNDRUG, GLORYx, SwissADME) kullanıldı. Bileşiklerin sitotoksik özellikleri, MCF7 (insan meme kanseri) hücre hattı ve HEK293 (insan sağlıklı embriyonik böbrek) hücre hattında in vitro analizler ile incelendi. Bileşiklerin COX-1 ve COX-2 enzim inhibisyon aktiviteleri tespit edildi.

Abstract:
In this thesis study, 15 new compounds were developed based on the 2,5-dichlorobenzohydrazide compound; 2,5-dichloro-N'-[(2-fluorophenyl)methylidene]benzohydrazide (3a), N'-[(2-bromo phenyl)methylidene]-2,5-dichlorobenzohydrazide (3b), N'-[(4-bromophenyl)methylidene]-2,5-dichlorobenzohydrazide (3c), 2,5-dichloro-N'-[(4-chlorophenyl)methylidene]-benzohydrazide (3d), 2,5-dichloro-N'-[(4-cyanophenyl)methylidene]-benzohydrazide (3e), 2,5-dichloro- N'-(4-hydroxybenzylidene)benzohydrazide (3f), 2,5-dichloro-N'-{[4-(methylsulfanyl)phenyl]methylidene}-benzohydrazide (3g), 2,5-dichloro-N'-[(4-nitrophenyl)methylidene]benzohydrazide (3h), 2,5-dichloro-N'-[(5-chloro-2-hydroxyphenyl(methylidene)]benzohydrazide (3i), 2,5-dichloro-N'-[(2,6-dichlorophenyl)methylidene]benzohydrazide (3j), 2,5-dichloro-N'-[(2,5-dimethoxyphenyl)methylidene]benzohydrazide (3k), N'-[(2H-1,3-benzodioxol-5-yl)methylidene]-2,5-dichlorobenzohydrazide (3l), 2,5-dichloro-N'-[(thiophen-2-yl)methylene)]benzohydrazide (3m), N'-[(5-bromo-1H-indol-3-yl)methylidene]-2,5-dichlorobenzohydrazide (3n), 2,5-dichloro-N'-{3-[4-(dimethylamino)phenyl]prop-2-ene-1-ylidene}benzohydrazide (3o) were synthesized. Structure determinations of the compounds were confirmed by elemental and spectroscopic methods (UV, IR, NMR (1H-NMR, 13C-NMR (APT), HSQC) ESI-MS). In addition, online programs (Shrödinger, XUNDRUG, GLORYx, SwissADME) were used to determine ADME, toxicological properties and metabolic Phase I and Phase II metabolites through in silico studies of the compounds. The cytotoxic properties of the compounds were examined by in vitro analyzes in MCF7 (the human breast cancer) cell line and HEK293 (the human healthy embryonic kidney) cell line. COX-1 and COX-2 enzyme inhibition activities of the compounds were determined.