Publication: Biyolojik aktif amino eter sentezleri
Abstract
BİYOLOJİK AKTİF AMİNO ETER SENTEZLERİ Daha önceki çalışmalardan n-Heptilaminlerin, Monoamin Oksidaz-B (MAO, E.C.1.4.3.4) nin iyi substratları olduğu bilinmektedir. Buna karşılık oksijen atomu içeren n-heptilaminin heteroatom içeren türevleri ise MAO-B'yi inhibe ettikleri tespit edilmiştir. Bu inhibisyonun detaylarını tespit etmek için bir seri alifatik yapıdaki amino eter bileşiği ilk defa bu çalışma kapsamında sentezlenmiştir. Sentezlenen bileşikler, 2-Butoksietilamin-p-Toluensülfonikasit tuzu (3) , 3-Propoksi-propilamin-p-Toluensülfonikasit tuzu (6) , 4-Etoksi-butilamin-p-Toluen sülfonik asit tuzu (9), 5-Metoksi-pentilamin-p-Toluensülfonikasit tuzu (12), N-Metil-2-Butoksi-etilamin-p-Toluensülfonikasit tuzu (13), N-Metil-3-propoksi-propilamin tartarik asit tuzu (16) ve N-Metil-5-metoksi-pentilamin tartarik asit tuzu (17) dur. Sentezlenen 3, 6, 9 ve 12 numaralı bileşiklerin içerdiği heteroatomun (Oksijen) indüktif etkisi MAO-B enzimi ile incelendi. Buna göre; bu bileşiklerin a-karbonlarından enzimin aktif bölgesine (muhtemelen sistin artığı) bağlanarak MAO-B'nin inhibisyona neden olduğu tespit edildi. Enzimatik çalışmaların sonucunda, enzim-ara ürün bileşiminin kararlılığı, oksijen atomu amin grubundan uzaklaştıkça azaldığı şeklinde saptandı. Sentezlenen bileşikler enzimin (MAO-B) biyolojik aktivitesini etkileyeceği veya değiştireceği için son derece önemlidir. Böylece, enzimin oksitlenme mekanizmasının daha detaylı bilinmesi, bu enzime karşı daha etkili ilaç tasarımını kolaylaştıracaktır.
THE SYNTHESIS OF BIOLOGICALY ACTIVE AMINO ETHERS In previous studies, it was found that n-heptylamines are very good substrates of Monoamine Oxidase B (E.C.1.4.3.4.). However,oxgen-containing n-heptylamine derivatives are the inhibitor of MAO-B. In order to determine the extent of this inhibition, a series of aminoether was synthesized in this study. The inductive effect of this heteroatom was investigated with the enzyme of MAO. The synthesized compounds are 2-Butoxyethylamine-p-Toluenesulfonic acid salt(3), 3-Propoxypropylamine-p-Toluenesulfonic acid salt (6), 4-Ethoxy- buthylamine-p-Toluenesulfonic acid salt (9), 5-Methoxypentylamine-p-Toluenesulfonic acid salt (12), N-Methyl-2-Butoxyethylamine-p-Toluenesulfonic acid salt (13), N-Methyl-3-propoxypropylamine tartaric acid salt (16) and N-Methyl-5-methoxypentylamine tartaric acid salt (17). It was established that the synthesized compounds 3,6,9,12 are causing inhibition of MAO-B by the attachment of the a-carbon atoms of the intermediates to the active sites residue (cystine residue most probably) of the enzyme MAO-B. It was observed that the stability of enzyme intermediate adduct decreased successively as the oxgen atom departed from the amino group. The synthesized compounds are very important since they will affect or change the biological activity of the enzyme. Thus, understanding the detail of the oxidation mechanism of this enzyme will facilitate the design of more effective drugs for MAO.
THE SYNTHESIS OF BIOLOGICALY ACTIVE AMINO ETHERS In previous studies, it was found that n-heptylamines are very good substrates of Monoamine Oxidase B (E.C.1.4.3.4.). However,oxgen-containing n-heptylamine derivatives are the inhibitor of MAO-B. In order to determine the extent of this inhibition, a series of aminoether was synthesized in this study. The inductive effect of this heteroatom was investigated with the enzyme of MAO. The synthesized compounds are 2-Butoxyethylamine-p-Toluenesulfonic acid salt(3), 3-Propoxypropylamine-p-Toluenesulfonic acid salt (6), 4-Ethoxy- buthylamine-p-Toluenesulfonic acid salt (9), 5-Methoxypentylamine-p-Toluenesulfonic acid salt (12), N-Methyl-2-Butoxyethylamine-p-Toluenesulfonic acid salt (13), N-Methyl-3-propoxypropylamine tartaric acid salt (16) and N-Methyl-5-methoxypentylamine tartaric acid salt (17). It was established that the synthesized compounds 3,6,9,12 are causing inhibition of MAO-B by the attachment of the a-carbon atoms of the intermediates to the active sites residue (cystine residue most probably) of the enzyme MAO-B. It was observed that the stability of enzyme intermediate adduct decreased successively as the oxgen atom departed from the amino group. The synthesized compounds are very important since they will affect or change the biological activity of the enzyme. Thus, understanding the detail of the oxidation mechanism of this enzyme will facilitate the design of more effective drugs for MAO.