Composition for protecting islet transplantation
The present invention pertains to a composition having a protective effect during islet transplantation, and more specifically, to a composition containing a compound of chemical formula 1 or a pharmaceutically acceptable salt thereof, and capable of providing a protective effect against oxidative stress, inflammation, etc. during islet transplantation.
1 . A method of protecting islets, comprising treating a pancreas during isolation of islets, or treating isolated islets during serum-deprived culture of isolated islets, with a compound of the following Formula 1 or a pharmaceutically acceptable salt thereof:
wherein
n is 0 or 1;
X is C and n is 1;
R 1 is hydrogen or C 1 -C 6 alkyl;
R 2 is phenyl;
R 3 is hydrogen or C 1 -C 6 alkyl;
R 4 is CH 2 -(1,1-dioxo-thiomorpholin-4-yl) or CH 2 -(2-oxopiperazin-4-yl);
R 5 is hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl; and
R 6 is tetrahydropyran or tetrahydrofuran,
wherein the compound of Formula 1 protects islets by reducing amounts of oxidative stress and reactive oxygen species (ROS).
2 . The method according to claim 1 , wherein the compound of Formula 1 is (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine of the following Formula 2:
3 . The method according to claim 1 wherein the compound of Formula 1 reduces the expression of c-jun N-terminal kinase, high mobility group box-1 (HMGB1), and and proinflammatory cytokines.
4 . The method according to claim 3 , wherein the proinflammatory cytokines are interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).
5 . The method according to claim 1 , wherein the compound of Formula 1 reduces the accumulation of amyloid and toxic islet amyloid polypeptide (IAPP) oligomers.