Predictive QSAR modeling study on berberine derivatives with hypolipidemic activity

Abstract

Berberine (BBR), isolated from a Chinese herb, is identified as a new cholesterol-lowering small molecule, and hundreds of berberine derivatives have been obtained for optimization of their hypolipidemic activities in recent years. However, so far there is no available quantitative structure-activity relationship (QSAR) model used for the development of novel BBR analogues with hypolipidemic activities, mainly due to lack of lipid-lowering molecular mechanisms and target identification of BBR. In this paper, the tactics using ligand efficiency indice instead of pIC as the activity could be adopted for the development of BBR QSAR models. A series of 59 BBR derivatives with hypolipidemic activities have been studied and split randomly into three sets of training and test sets. Statistical quality of most building models shows obviously robust. Best calculated model that employs LLE indice as the activity (Model 6) has the following statistical parameters: for training set R = .984, Q = 0.981, RMSE = 0.1160, and for test set R = .989, RMSE = 0.0067. This model would be used for the development of novel BBR analogues with lipid-lowering activities as a hit discovery tool.

A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

“…Berberine (BB) is an isoquinoline alkaloid originally isolated from Chinese herb Coptis chinensis (Huang lian), which exerts anti‐diabetic and anti‐inflammatory activities . Over the past decades, a number of experimental and clinical studies have been centralized on the biological activities of Metformin, Berberin and their derivatives . However, little information is available on the synthesis of novel compounds containing Metformin and Berberin derivatives.…”

“…[17][18][19] Over the past decades, a number of experimental and clinical studies have been centralized on the biological activities of Metformin, Berberin and their derivatives. [20][21][22][23][24][25][26][27] However, little information is available on the synthesis of novel compounds containing Metformin and Berberin derivatives. Our group has designed and synthesized the novel compound BMH473.…”

Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives

“…Berberine is a natural molecule present in some medicinal plants, mainly of the Berberidaceae family ( Berberis aquifolium , B. aristata , B. asiatica , B. chitria , B. lyceum , B. vulgaris ) but also in other species such as Argemone mexicana , Coptis japonica , Hydrastis canadensis , Papaver dubium , Thalictrum flavum [ 3 ]. Berberine and its derivatives [ 4 ] are known for having various biological activities such as antimalarial [ 5 ], antileishmanial [ 6 ], antiviral [ 7 , 8 ], hypolipidemic [ 9 ], anticancer [ 10 , 11 ] and antimicrobial effects [ 12 , 13 , 14 ]. Most of the active derivatives of berberine were obtained by substitution of various group at the position 9 and/or 13 resulting in higher activities compared to the parent molecule.…”

Discovery of 7,9-Disulfatetrahydroberberine as Novel Lipid-Lowering Agents

“…Based on this situation, a robust QSAR model of BBR used for predicting hypolipidemic activity was developed via computer-aid design means, 12 and meanwhile, dozens of BBR derivatives were designed and synthesized in our laboratory. The results from screening assay showed that 9- O -phenylsulfonylberberine ( Figure 2 , compound a ) displayed potent activity (data not shown).…”