INHIBICIJA KSANTIN OKSIDAZE DERIVATIMA 1,2,3,4-TETRAHIDROIZOHINOLINA
Sažetak
Ksantin oksidaza (XO) je metaloflavoproteinski enzim koji je najpoznatiji po svojoj ulozi ograničavanja brzine razgradnje purinskih nukleotida. Terapijska inhibicija XO se zasniva na njenoj ulozi u brojnim bolestima koje su povezane bilo sa hiperprodukcijom mokraćne kiseline ili hiperprodukcijom reaktivnih kiseoničnih vrsti. U ovom radu je izvršeno ispitivanje sposobnosti inhibicije XO 24 derivata 1,2,3,4-tetrahidroizohinolina, od kojih je jedinjenje 16 pokazalo IC50 vrednost od 135,72 ± 2,71 µM. Interakcija jedinjenja 16 sa XO enzimom je simulirana korišćenjem Site Finder modula, molekularnog docking-a i molekularne dinamike. Molekularni modeling ukazuje da su interakcije sa Met 1038, Gln 1040, Thr 1077, Gln 1194 i Val 1259 važan faktor postojanja afiniteta inhibitora prema XO enzimu. Naš predloženi model vezivanja bi mogao biti od značaja za razvoj novih aktivnih inhibitora XO zasnovanih na 1,2,3,4-tetrahidroizohinolinskom heterociklusu.
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