DESIGN AND SYNTHESIS OF SOME ARYLHYDRAZONE DERIVATIVES AS POTENTIAL FAAH INHIBITORS

Yıl 2023, Cilt: 47 Sayı: 1, 111 - 119, 20.01.2023

Zehra Tuğçe Gür Maz Sümeyye Turanlı H. Burak Calıskan

https://doi.org/10.33483/jfpau.1181948

Öz

Objective: The aim was to design, synthesis and investigation of possible interactions in the enzyme active site of a series of arylhydrazone derivatives for the inhibition of the FAAH enzyme.”

Material and Method: Arylhydrazone derivatives were obtained through the reaction of nicotinic hydrazide or benzohydrazide with appropriate aldehyde derivatives, and the obtained crude product was recrystallized from ethanol. After elucidating chemical structures of the compounds via spectroscopic methods, the inhibitory activities against hFAAH were screened. The results were further supported with molecular modeling studies.

Result and Discussion: In this study, a new series of seven arylhydrazone derivatives were screened against hFAAH. 4-phenoxyphenyl bearing derivative 5 was found to inhibit hFAAH 40 % at 10 µM which indicates that newly developed inhibitor could serve as a starting point for improving inhibitory effect of the new series.

Anahtar Kelimeler

Arylhydrazones, FAAH, heterocycles, inflammation

Destekleyen Kurum

Gazi University Scientific Research Project Unit

Proje Numarası

BAP: 02/2020-24

Teşekkür

The authors would like to thank Prof. Dr. Burcu Caliskan for providing her expertise in this research. This research is financially supported by Gazi University Scientific Research Project Unit (BAP: 02/2020-24).

POTANSİYEL FAAH İNHİBİTÖRÜ OLARAK BAZI ARİLHİDRAZON TÜREVİ BİLEŞİKLERİN TASARIMI VE SENTEZİ

Öz

Amaç: FAAH enziminin inhibisyonu amacıyla bir seri arilhidrazon türevi bileşiğin tasarımı, sentezi ve enzim aktif bölgesinde olası etkileşimlerinin incelenmesidir.

Gereç ve Yöntem: Nikotinik hidrazit veya benzohidrazidin uygun aldehit türevleri ile reaksiyonu sonucu arilhidrazon türevleri elde edilmiş, elde edilen ham ürünler etanolden rekristalize edilmiştir. Bileşiklerin yapısı spektroskopik yöntemler ile aydınlatıldıktan sonra hFAAH enzimine karşı aktiviteleri taranmıştır. Elde edilen sonuçlar moleküler modelleme çalışmaları ile desteklenmiştir.

Sonuç ve Tartışma: Bu çalışmada, bir seri yedi arilhidrazon türevi hFAAH'a karşı taranmıştır. 4-fenoksifenil içeren türev olan Bileşik 5'in 10 uM'de hFAAH'ı % 40 oranında inhibe ettiği bulunmuş olup; ileri çalışmalarda potansiyel hFAAH inhibitörü olarak kullanılabilecek yeni bir arilhidrazon türevine ulaşılmıştır.

Anahtar Kelimeler

Arilhidrazonlar, FAAH, heterosiklikler, inflamasyon

Proje Numarası

BAP: 02/2020-24

Kaynakça

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