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.

中文翻译：

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作为抗衰老药的丙酸梓醇的设计，合成和初步生物学评估

本文利用Surflex-Docking方法，基于分子对接（MD），设计了谷胱甘肽丙酰化类似物（CPs）作为谷胱甘肽过氧化物酶（GSH-Px）的药物配体。计算出的CP的总分（Total_score）和C log P均高于catalpol，这表明CP可作为潜在的先导化合物用作新的抗衰老药物。此外，一组CP中异构体的最大Total_score通常不是具有最小能量结构的分子。这些表明，与GSH-Px对接的CP不仅受分子能的影响，而且还受其构象的影响。以吡啶为溶剂，以苯丙氨酸为反应剂，以DMAP为催化剂，在特定温度下反应，用丙酸酐将梓醇与丙酸酐进行酯化反应，合成了CP。通过NMR，FT-IR，HRMS和HPLC测定合成的全丙酰化的梓醇类似物（CP-6），并通过正交实验设计优化了合成工艺。随后，通过MTT分析筛选了CP-6的细胞活力，结果表明CP-6可以有效逆转STZ诱导的细胞活力降低，并且CP-6具有潜在的抗衰老活性。