Study on Synthesis of Cinnamic Acid Analogues and Their Anti-diabetic Activity
Objective To synthesize cinnamic acid analogues and investigate their anti-diabetic activity and mechanism. Methods With different substituted benzaldehyde and acetic anhydride as raw material,potassium acetate as catalyst,cinnamic acid analogues were synthesized through Perkin reaction. Then,their protective effects on islet β cells were tested under the stimulation of palmitic acid (PA). Furthermore,the anti-diabetic mechanism of the dominant compounds was explored. Results Ten target compounds showed varying degrees of protection against islet β cells,and compounds RG-1 and RG-4 exhibited strong cytoprotection. The cell survival rate was 97.19％ and 89.68％,respectively. Molecular mechanism studies showed that compounds RG-1 and RG-4 could reduce the generation of intracellular reactive oxygen species,inhibit the expression of thioredoxin-interacting protein (TXNIP) protein,decrease malondialdehyde (MDA) content and cysteine aspartase 3 (caspase 3) activity,as well as increase superoxide dismutase(SOD)activity. Furthermore,RG-1 and RG-4 exhibited favorable pharmacokinetic properties. Conclusion A total of 10 cinnamic acid analogues (RG1～RG10) were synthesized in this study. RG-1 and RG-4 exerted strong protective effects on islet β cells by inhibiting oxidative stress. RG-1 and RG-4 are potential anti-diabetic molecules.
cinnamic acid analoguesdiabetesislet β-cellsantioxidantmechanism of actiondrug-like propertypharmacokinetics
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维普
