Design, microwave synthesis, and molecular docking studies of catalpol crotonates as potential neuroprotective agent of diabetic encephalopathy

Abstract

Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.

Terpenoid natural products exert neuroprotection via the PI3K/Akt pathway

“…Therefore, chemical modification of its derivatives must result in improved bioavailability. Liu et al (2020) used computer-aided drug design (CADD) to dock catalpol crotonates with glutathione peroxidase (GSH-Px) which has neuroprotective properties. By using microwave-assisted synthesis (MWAS) as a synthesis method, they were successful in designing and synthesizing catalpol hexacrotonate (CC-6).…”

Study on the chemical reactivity difference of primary hydroxyl groups in iridoid glycosides

“…In order to modify the hydroxyl groups in iridoid glycosides, it is necessary for researchers to study this. According to the researches on iridoid glycosides previously reported by our research group [20][21][22] , computer simulation was used to explore the difference between the C10-position and C6 ′ -position primary hydroxyl groups, and experiments were used to verify the difference and control the reaction conditions to generate a single product in order to obtain the higher yield in this paper.…”