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

Abstract

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.

Keywords

• 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

Abstract

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.

Keywords

• Rivastigmine,galantamine,inhibition,carbonic anhydrases

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