Synthesis and biological activities of some aryl (alkyl)azole derivatives

Abstract

Aryl (alkyl) azole group compounds have antifungal, anticonvulsant and antibacterial activities. Inhibition of heme oxygenase, indolamine 2,3-dioxygenase-1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is evident in the literature. There are also reports that compounds containing this aryl (alkyl) azole group, which are currently used in fungal infections, and activate antioxidant systems in vivo. In this study, 2-(1H-1,2,4-triazole-1-yl)-1-(2,4-dichlorophenyl) ethanol and three new aromatic side chain ester derivatives were synthesized based on the aryl (alkyl) azole structure. Four imidazole derivatives based on the aryl (alkyl) azole structure which were synthesized in another study and molecules in this study were evaluated for AChE and BChE enzyme inhibition and antioxidant activities. While enzyme inhibition were evaluated with Ellman’s modified method, antioxidant activities were evaluated with DPPH and FRAP methods. In this study synthesized molecules’ structure were elucidated with IR, ¹H-NMR, ¹³C-NMR and LC-MS spectral analysis. While no activity was observed in the 1,2,4-triazole derivatives both for enzyme inhibition and antioxidant activity, in the imidazole derivative compounds low activity for enzyme inhibition and DPPH radical scavenging activity was observed. In FRAP method there were no activity in imidazole derivatives. While IC₅₀was more concentrated than 1000 µMfor imidazole, standard Galantamin’s IC₅₀ value was21.30 and 37.03 µM for enzyme inhibition. For antioxidant activity, standard Gallic acid IC 50 was68.83 µM and imidazole derivatives IC₅₀ were more concentrated than 1000 µM. The absence of activity of our compounds suggests that large structures such as the aromatic ring in the side chain may be effective in enzyme interaction. We plan to synthesize new derivatives bearing alkyl (saturated, unsaturated, halogen substituents, etc.) groups in the side chain in the aryl (alkyl) azole group compounds and evaluate AChE and BChE enzyme inhibition and antioxidant activities.

Keywords

• Aryl(alkyl)azole,antioxidant,4-triazole,1 2 4-triazole

Aril(alkil)azol türevlerinin sentezi ve biyolojik aktiviteleri

Abstract

Aril(alkil)azol grubu bileşikler antifungal, antikonvülsan, antibakteriyel aktivitelere sahiptir. Hem oksijenaz enzim inhibisyonu, indolamin 2,3-dioksigenaz-1 enzim inhibisyonu, asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BChE) enzim inhibisyonu aktivitelerinin değerlendirildiği çalışmalar da mevcuttur. Bu çalışmada, aril (alkil) azol yapısında, 2(1H-1,2,4-triazol-1-il)-1-(2,4-diklorofenil) etanol bileşiği ve bu bileşikten hareketle üç adet yeni aromatik yan zincir içeren ester türevleri sentezlendi. Başka bir çalışmada sentezlenen yapısında triazol yerine izosteri olan imidazol halkası taşıyan, dört adet bileşik ve bu çalışmada sentezlenen bileşiklerin AChE ve BChE enzim inhibisyonu Ellman metodunun modifiye şekli ile değerlendirilirken, antioksidan aktivitesi 1,1-difenil-2-pikrilhidrazil (DPPH) radikal süpürücü aktivite yöntemi ile değerlendirildi. Sentezlenen yeni bileşiklerin yapıları IR, ¹H-NMR, ¹³C-NMR ve LC-MS spektroskopik yöntemlerle kanıtlandı. 1, 2, 4-Triazol türevlerinde herhangi bir aktivite görülmezken, imidazol türevi bileşiklerde AChE enzim inhibisyonu ve DPPH radikal süpürücü aktivite gözlenmiştir. İmidazol türevlerinde enzim inhibisyonu aktiviteler IC₅₀ (%50 inhibitör derişimi) değeri 1000 µM’dan yüksek derişimlerde iken, standart olan Galantamin bileşiğinde IC₅₀ değeri 21.30 µM ve 37.03 µM’da gözlenmiştir. Antioksidan aktivite, standart olan gallik asit için IC₅₀ 68.83 µM iken, imidazol türevlerinde IC₅₀ 1000 µM’dan yüksek derişimlerde gözlenmiştir. Bileşiklerde aktivite gözlenmemesi, yan zincirdeki aromatik halkanın enzim etkileşiminde sterik engel oluşturduğunu düşündürmüştür. Aril (alkil) azol grubu bileşiklerde, yan zincirde alkil (doymuş, doymamış, halojenli sübstitüe vb) grubu taşıyan yeni türevler sentezlenerek bu aktivitelerin değerlendirilmesi planlanmaktadır. 

Keywords

• 4-triazol,Aril (alkil) azol,antioksidan,AChE ve BChE enzim inhibisyonu,1 2 4-triazol

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