MODULACIJA AKTIVNOSTI ACETILHOLINESTERAZE POLIOKSOVOLFRAMATIMA
Sažetak
Uvod: Alchajmerova bolest ima svoju patoanatomsku osnovu. U oboljenju dominira gubitak sinapsi i neurona što dovode do poremećaja na neurotransmiterskim sistemima mozga, pre svega na nivou acetilholinskog transmiterskog sistema. Polioksometalati (POM), kao visoko potentni i selektivni inhibitori acetilholinesteraze (AChE), enzima odgovornog za razgradnju acetilholina, pronalaze potencijalnu primenu u terapiju Alchajmerove bolesti, jer bi se time povećalo i produžilo delovanje nedostajućeg acetilholina.
Cilj rada: Ispitivanje in vitro uticaja POM-a na aktivnost AChE.
Materijal i metode: U našem istraživanju ispitivan je uticaj pet novosintetisanih heteropolioksovolframata: 1) K6[PV3W9O40] x 3H2O, 2) K6H2[TiW11CoO40] x 13H2O, 3) (NH4)14[NaP5W30O110] x 31H2O, 4) K7[SiV3W9O40] x 10H2O i 5) K7[Ti2PW10O40] x 10H2O na aktivnost acetilholinesteraze. Aktivnost AchE merena je modifikovanom Elmanovom (Ellman) metodom.
Rezultati: Ispitivana jedinjenja inhibiraju aktivnost AChE na dozno zavisan način u ispitivanom opsegu koncentracija. Dobijeni inhibicioni parametri pokazuju da su jedinjenja 2, 3 i 5 veoma potenti inhibitori enzimske aktivnosti i da su izračunate IC50 vrednosti ovih polioksovolframata u oblasti submikromolarnih i mikromolarnih koncentracija. S druge strane, jedinjenja 1 i 4 pokazala su oko sto, odnosno hiljadu puta slabije inhibitorno dejstvo na aktivnost AChE u poređenju sa najpotentnijim inhibitorom (jedinjenje 3) čija IC50 vrednost iznosi 4,79×10-7 mol/L. Dobijeni rezultati su u saglasnosti sa ranije pokazanim inhibitornim efektom polioksovolframata na aktivnost holinesteraza.
Zaključak: Prema dobijenim rezultata možemo da zaključimo da ispitivani polioksometalati na fiziološkoj pH vrednosti inhibiraju aktivnost AChE, kao i da je dobijena inhibicija dozno-zavisna. Inhibitorne moći POM testiranih u ovom radu se međusobno značajno razlikuju, što je verovatno posledica razlika u naelektrisanju, veličini i obliku ovih poliokosmetalata.
Ključne reči: Alchajmerova (Alzheimer) bolest, polioksometalati, acetilholinesteraza,
inhibicija
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