An Investigation on the Quantitative Structure-Activity Relationships of the Anti-Inflammatory Activity of Diterpenoid Alkaloids.

Xiao Li,Zhenyu Sui,Kaishun Bi,Ning Li,Zuojing Li

doi:10.3390/molecules22030363

Xiao Li, Zhenyu Sui + Show 3 more

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https://doi.org/10.3390/molecules22030363

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Abstract

Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of studies focused on the determination, quantitation and pharmacological properties of these alkaloids has increased dramatically during the past few years. In this work we built a dataset composed of 15 diterpenoid alkaloid compounds with diverse structures, of which 11 compounds were included in the training set and the remaining compounds were included in the test set. The quantitative chemistry parameters of the 15 diterpenoid alkaloids compound were calculated using the HyperChem software, and the quantitative structure–activity relationship (QSAR) of these diterpenoid alkaloid compounds were assessed in an anti-inflammation model based on half maximal effective concentration (EC50) measurements obtained from rat paw edema data. The QSAR prediction model is as follows: (R2 = 0.981, Q2 = 0.92). The validated consensus EC50 for the QSAR model, developed from the rat paw edema anti-inflammation model used in this study, indicate that this model was capable of effective prediction and can be used as a reliable computational predictor of diterpenoid alkaloid activity.

Highlights

The diterpenoid alkaloids are found in many traditional herbal medicines (TCM), such as Consolida, Aconitum, and Delphinium
The relationship between the structure and activity is determined by the structure-activity relationship, in order to modify the structure of the compounds and enhance the anti-inflammatory activity [2], we studied the relationship between the activity and structure of the diterpenoid alkaloids
The relationship between Log(EC50 ) and 10 variables modeled by Partial least squares (PLS) was as follows: log( EC50 ) = −0.0260 × SAA + 0.0086 × surface area grid (SAG) + 0.0011 × VOL − 0.0641 × hydration energy energy (HE)

Summary

Introduction

The diterpenoid alkaloids are found in many traditional herbal medicines (TCM), such as Consolida, Aconitum, and Delphinium. Pharmacological studies have indicated that many diterpenoid alkaloids are important chemical constituents of this herbal remedies with analgesic, anti-cancer, anti-inflammatory, and anti-arrhythmic activities [1]. The anti-inflammatory activity was the first confirmed important pharmacological activity of the diterpenoid alkaloids, and is stronger than that of many active anti-inflammatory drugs [2]. Most of the diterpenoid alkaloids are isolated from Aconitum, Consolida and Delphinium species, which have been widely used in medicine with excellent clinical efficacy for thousands of years. There are three categories of diterpenoid alkaloids containing 18, 19 and 20 carbon atoms, respectively, which are classified as the C18-, C19-, and C20-diterpenoid alkaloids [3].

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