Synthesis of phenylacetamide derivatives and their protective effects on islet cell damage induced by palmitic acid
- VernacularTitle:苯乙酰胺衍生物的合成及其对棕榈酸诱导的胰岛细胞损伤的保护作用
- Author:
Ai-Yun LI
1
;
Li GUAN
;
Wan-Zhen SU
;
Yang-Yang LU
;
Sheng-Jie ZHANG
;
Wei-Ze LI
;
Xiang-Ying JIAO
Author Information
- Keywords: diabetes; thioredoxin interaction protein; phenylacetamide derivatives; oxidative stress; NLRP3 inflammasome; islet cell protection
- From: Chinese Pharmacological Bulletin 2024;40(6):1130-1136
- CountryChina
- Language:Chinese
- Abstract: Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.
