İMİDAZOLİNON BAZLI SÜLFONAMİD TÜREVLERİ: SENTEZ, KARAKTERİZASYON VE BAZI METABOLİK ENZİMLERE KARŞI İNHİBİTÖR ÖZELLİKLERİ

Öz

Amaç: Çalışmanın amacı, güçlü ve seçici enzim inhibitörleri olarak imidazolinon bazlı sülfonamid türevlerinin yeni sentetik bileşiklerini araştırmaktır. Sentezlenen bir dizi bileşik ve bunların asetilkolin esteraz (AChE) ve insan (h) karbonik anhidraz (CA) izoformları I ve II'ye karşı inhibe edici etkileri araştırılmıştır. Gereç ve Yöntem: Bileşiklerin yapısı HRMS, 1H ve 13C NMR ile doğrulanmıştır. Bileşiklerin farmakolojik potansiyeli, in vitro enzim bazlı analizler ile belirlenmiştir. Sonuç ve Tartışma: Bu çalışmada, imidazolinon bazlı sülfonamit bileşikleri serisi 4-(2,4-dimetoksibenziliden)-2-feniloksazol-5(4H)-on, sodyum asetat, buzlu asetik asit ve sulfaguanidin (3), sulfanilamid (4), sulfadiazin (5) gibi uygun sülfonamid türevlerinden hareketle sentezlendi. Bu bileşikler, asetilkolin esteraz (AChE) ve insan (h) karbonik anhidraz (CA) izoformları I ve II'ye karşı güçlü inhibe edici etki gösterdi. Bileşik 4 (Ki= 19.53±1.23 nM), hCA I'e karşı güçlü ve seçici bir inhibitör iken, bileşik 3'ün (Ki=16.49±2.20 nM) hCA II'ye karşı güçlü inhibitör olduğu bulundu. 11.68±1.45 nM Ki'ye sahip bileşik 5, AChE enzimine karşı güçlü bir inhibitör etki gösterdi. İmidazolinon bazlı sülfonamidler, seçici CA inhibitörleri ve anti-Alzheimer bileşiklerinin tasarımında ileriki çalışmalarda kullanılabilirler.

Anahtar Kelimeler

• İmidazolin
• sentez
• asetilkolinesteraz
• karbonik anhidraz
• Alzheimer hastalığı

IMIDAZOLINONE-BASED SULFONAMIDE DERIVATIVES: SYNTHESIS, CHARACTERIZATION, AND INHIBITORY PROPERTY AGAINST SOME METABOLIC ENZYMES

Öz

Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-(2,4-dimethoxybenzylidene)-2-phenyloxazol-5(4H)-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine (3), sulfanilamide (4), sulfadiazine (5). These compounds showed potent inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II. Compound 4 (Ki=19.53±1.23 nM) was a potent and selective inhibitor against hCA I while compound 3 (Ki=16.49±2.20 nM) was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.68±1.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimer's compounds for further studies.

Anahtar Kelimeler

• İmidazolinone
• synthesis
• acetylcholinesterase
• carbonic anhydrase
• Alzheimer’s disease

Kaynakça

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