Benzoksazolon Türevi Şalkon Bileşiklerinin Sentezi ve Biyoaktivitelerinin Araştırılması

Bu çalışmada, genel kimyasal yapısı 6-(3-Aril-2-propen-1-oil)-2(3H)-benzoksazolon olan ve aril kısmı benzen, furan veya tiyofen olarak tasarlanan üç adet bileşik başarıyla sentezlenmiş ve yapıları 1H NMR, 13C NMR ve HRMS spektrumları ile aydınlatılmıştır. Bileşik 2, 6-[3-(Furan-2-il)-2-propen-1-oil]-2(3H)-benzoksazolon, sentezi ile ilk kez bu çalışmada rapor edilmiştir. Sentezlenen bileşiklerin sitotoksik aktiviteleri (bileşik 1 hariç), karbonik anhidraz inhibitör aktiviteleri (1-3) ve asetilkolin esteraz inhibitör aktiviteleri (1-3) ise ilk kez bu çalışma ile rapor edilmiştir. Bileşiklerin tümünün AChE enzim inhibitör aktiviteleri referans bileşikten yüksekken, sitotoksik ve hCA I/II inhibitör aktiviteleri referans bileşiklerden düşüktür. Yalnızca bileşik 2, referans bileşik AZA’ya benzer hCA I inhibisyon göstermiştir. Ayrıca, bileşiklerin aril kısmına fenil halkasının getirilmesinin, tiyofen veya furan halkasına göre, sitotoksik ve AChE enzim inhibitör aktiviteleri açısından daha faydalı bir modifikasyon olduğu bu çalışma ile ortaya konulmuştur. Bundan başka, sentezlenen bileşiklerin yüksek AChE inhibitör aktiviteleri nedeniyle ileriki çalışmalar için uygun öncü bileşikler oldukları görülmüştür.

Anahtar Kelimeler:

Asetilkolin esteraz, benzoksazolon, karbonik anhidraz, şalkon, sitotoksisite

Synthesis and Bioactivities of Benzoxazolone Derivative Chalcone Compounds

In this study, three compounds, 6-(3-aryl-2-propen-1-oyl)-2(3H)-benzoxazolones, whose aryl part is designed as benzene, furan or thiophene were synthesized successfully and their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. Compound 2, 6-[3-(Furan-2-yl)-2-propen-1-oyl]-2(3H)-benzoxazolone, was reported for the first time with its synthesis in this study. Cytotoxic activities (except compound 1), carbonic anhydrase inhibitory activities (1-3) and acetylcholine esterase (AChE) inhibitory activities (1-3) of synthesized compounds were reported for the first time in this study. The AChE enzyme inhibitory activities of all compounds were higher than the reference compound, while the cytotoxicities and hCA I/II inhibitory activities of the compounds were lower than the reference compounds. Only compound 2 showed similar inhibitory activity with reference drug AZA against hCA I. Furthermore, in this study, it was shown that introducing the phenyl ring as the aryl moiety of the compounds was a more useful modification than the thiophene or furan rings in terms of the cytotoxic and AChE enzyme inhibitory activities. On the other hand, all synthesized compounds were found to be as candidate molecules for further studies due to their high AChE inhibitory activities.

Keywords:

Acetylcholinesterase, benzoxazolone, carbonic anhydrase, chalcone, cytotoxicity,

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