Design and synthesis of 4-phenylbutyric acid analogues and their inhibition effect on the endoplasmic reticulum stress and over-autophagy in PC12 cells
FAN Lanlan, KONG Shanshan, WU Binbin, YE Xiaoxia
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
FAN Lanlan,KONG Shanshan,WU Binbin, et al. Design and synthesis of 4-phenylbutyric acid analogues and their inhibition effect on the endoplasmic reticulum stress and over-autophagy in PC12 cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2021, 51(8): 615-622.
Abstract：Objective: To design and synthesize 4-phenylbutyric acid (PBA) analogues and explore their dual inhibition effect on the endoplasmic reticulum stress (ERS) and excessive autophagy in PC12 cells.Methods: Compounds (A1-A11) were designed and synthesized based on the structure of PBA whose chemical structures were confirmed by 1H NMR, 13C NMR and MS. MTT was used to analyze the protective effect of A1-A11 on endoplasmic reticulum injury model of PC12 cells induced by TG and injury model of PC12 cells induced by H2O2; Western blot was used to measure the levels of glucose regulated protein 78 (GRP78),LC3 II/I and Beclin-1. Results: Compounds A3, A5, A7 and A9-A11 were new compounds. MTT assay showed that A1 displayed good protective effect on endoplasmic reticulum stress injury model (P<0.05). A1, A2, A4 and A6-A10 indicated great protective effect on autophagy injury model (P<0.05). Western blot showed that A1 could significantly inhibit the expression of GRP78, LC3 II/I and Beclin-1 (P<0.05). Conclusion: Compared with PBA,A1 performs excellent dual protective effect on ERS and autophagy injured model.
