Alzheimer Hastalığı Tedavisinde Kullanılan Rivastigmin ve Galantamin İlaç Etken Maddelerinin CA I ve II İzoenzimleri Üzerine in vitro Etkilerinin İncelenmesi

Yıl 2017, Cilt: 10 Sayı: 1, 1 - 10, 28.06.2017

Esra Dilek , Murat Çankaya , Talat Ezmeci Mukadder Sunar T. Abdulkadir Çoban

Öz

Karbonik anhidraz (CA, EC.4.2.1.1), CO₂’in,
HCO₃^- ve H⁺ iyonlarına iki basamakta dönüşümlü
hidratasyonunu katalizleyen, çinko (Zn²⁺) iyonlu metallo enzimlerden
biridir. Fizyolojik ve patolojik birçok proseste önemli rol oynar. Bu
çalışmanın amacı, Alzhaimer hastalığının tedavisinde kullanılan bazı ilaç etken
maddelerinin insan eritrosit CA I ve II izoenzimleri üzerine in vitro
etkilerini araştırmaktır. İnsan kanından CA-I ve II izoenzimleri Sefaroz-4B-L-tirozin-sülfamid
afinite kromotografisi yöntemi ile saflaştırıldı. CA I izoenzimi: yaklaşık %
61.7 verimle 122.2 kat; CA II izoenzimi: % 60 verimle 807.5 kat
saflaştırılmıştır. CA I için rivastigmin yarışmalı inhibisyon, galantamin ise
yarışmasız inhibisyon gösterdi. CA II için ise her iki etken madde de
yarışmasız inhibisyon gösterdi. K_i değerleri ise rivastigmin için CA
I: 0.79 µM; CA II: 1.08 µM, galantamin için CA I: 0.41µM; CA II: 0.40 µM olarak
hesaplandı. Elde edilen sonuçlara bakıldığında en kuvvetli inhibitör galantamin
olarak tespit edildi.

Anahtar Kelimeler

Rivastigmin, galantamin, inhibisyon, karbonik anhidraz

Investigation in vitro Effects of Rivastigmine and Galantamine Used to Treatment of Alzheimer's Disease on CA Isozymes I and II

Öz

The carbonic
anhydrases (CA, EC. 4.2.1.1) are an expanding family of zinc-containing enzymes
catalyzing the reversible hydration of CO₂ in a two-step reaction to
yield HCO₃^-and H⁺. These enzymes play
important roles in several physiological/pathological processes. The aim of
this study is to evaluate in vitro
the effects of these drug active substances which use which use for treatment
of Alzheimer disease on CA I and II isoenzyme. CA I and II isoenzymes from
human blood have been purified using Sepharose-4B-l-tyrosine-sulfanilamide
affinity chromatography method. The CA I isoenzyme was purified ~122.2-fold
with a yield of 61.7%. The CA II isoenzyme was purified ~807.5-fold with a
yield of 60%. rivastigmine was showed competitive inhibition and galantamine
was showed uncompetitive inhibition for CAI. Both of these drug active
substances were showed uncompetitive inhibition for CAII. K_i values
were determined for rivastigmine CA I: 0.79 µM; CA II: 1.08 µM and for
galantamine CA I: 0.41µM; CA II: 0.40 µM.
The results obtained in this study galantamine was identified as the most
potent inhibitor.

Anahtar Kelimeler

Rivastigmine, galantamine, inhibition, carbonic anhydrases

Kaynakça

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