Design, synthesis, and preliminary biological evaluation of catalpol propionates as antiaging drugs

Chunhong Dong,Qiang Wang,Guoqing Wang,Shuanglin Liu,Xiaodong Cheng,Shiqing Jiang

doi:10.1186/s13065-019-0626-3

Abstract

In this paper, catalpol propionylated analogs (CPs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surflex-Docking method. The calculated total scores (Total_score) and C log P of CPs are higher than that of catalpol, which show that the CPs maybe served as potential lead compounds as new antiaging drugs. Furthermore, the maximum Total_score of isomers in one group CPs is often not that the molecule with minimum energy structure. These show that the CPs docking with GSH-Px maybe not only affected by the molecular energy, but also affected by their conformations. The CPs were synthesized by esterification of catalpol with propionic anhydride using pyridine as solvent and acid banding agent, DMAP as catalyst, reaction at specific temperature. The synthesized perpropionylated catalpol analog (CP-6) was determined by NMR, FT-IR, HRMS, and HPLC, and the synthesis process was optimized by means of orthogonal experimental design. Subsequently, CP-6 was screened for cells viability by MTT assay, the results show that the CP-6 can effectively reversed STZ-induced reduction of cells viability, and CP-6 has potential antiaging activity.

Highlights

Aging is closely associated with diverse chronic diseases, such as hypertension, diabetes, and multiple cancers, etc. [1,2,3]
In order to improve its blood–brain barrier and fast metabolism, one to six of the hydroxyl groups were designed to be propionylated as catalpol propionylated analogs (CPs)
These results indicate that propionylation can improve the antiaging activity of catalpol analogs, and maybe that CP-6 is the best one

Summary

Introduction

Aging is closely associated with diverse chronic diseases, such as hypertension, diabetes, and multiple cancers, etc. [1,2,3]. Aging is closely associated with diverse chronic diseases, such as hypertension, diabetes, and multiple cancers, etc. With the trend of global aging and the improvement of living standards, health problems caused by aging and aging-associated diseases have become increasingly prominent [2, 3]. It is well accepted that the most significant determinant of aging is oxidative damage caused by overproduction of reactive oxygen species (ROS) [4,5,6]. There is no reported that catalpol used as clinical drug in the treatment of age-related diseases because of its blood–brain barrier caused by low lipophilicity and fast metabolism in body [9]. It is necessary to improve its lipophilicity, reduce its blood–brain barrier, increase its utilization in vivo, and modify its structure for used as antiaging drugs

Methods

Results

Conclusion