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

Yıl 2019, Cilt: 12 Sayı: 1, 60 - 71, 28.04.2019

Mefkure Durmuş , Burak Barut Arzu Özel , Erdinç Sellitepe , İnci Selin Doğan

https://doi.org/10.26559/mersinsbd.419125

Öz

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.

Anahtar Kelimeler

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

Aril(alkil)azol türevlerinin sentezi ve biyolojik aktiviteleri

Öz

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. 

Anahtar Kelimeler

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

Kaynakça

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