Research Article: Computational Analysis of Gynura bicolor Bioactive Compounds as Dipeptidyl Peptidase-IV Inhibitor

Date Published: August 8, 2017

Publisher: Hindawi

Author(s): Lina Rozano, Muhammad Redha Abdullah Zawawi, Muhamad Aizuddin Ahmad, Indu Bala Jaganath.

http://doi.org/10.1155/2017/5124165

Abstract

The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of Gynura bicolor in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of G. bicolor bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors. Evaluation of G. bicolor bioactive compounds for potent DPPIV inhibitors was computationally conducted using Lead IT and iGEMDOCK software, and the best free-binding energy scores for G. bicolor bioactive compounds were evaluated in comparison with the commercial DPPIV inhibitors, sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin. Drug-likeness and absorption, distribution, metabolism, and excretion (ADME) analysis were also performed. Based on molecular docking analysis, four of the identified bioactive compounds in G. bicolor, 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and trans-5-p-coumaroylquinic acid, resulted in lower free-binding energy scores when compared with two of the commercially available gliptin inhibitors. The results revealed that bioactive compounds in G. bicolor are potential natural inhibitors of DPPIV.

Partial Text

Type-2 diabetes is a chronic metabolic impairment that affects the quality of life. Currently, diabetes is ranked as the eighth leading cause of death with 1.5 million deaths, and 90% of these are from type-2 diabetes [1]. The main cause of type-2 diabetes is excessive blood glucose and the inability of the body to produce enough insulin, also known as insulin resistance in insulin-targeting tissues such as liver, skeletal muscle, and adipocytes. The body’s resistance to insulin causes glucose to remain in the blood, further damaging other organs owing to the high level of sugar, which leads to loss of vision, kidney failure, and cardiovascular diseases.

This study reported three major findings: (1) the identification of three major compounds, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and cis-5-p-coumaroylquinic acid, not yet reported before in G. bicolor; (2) the prediction of lower free-binding energy scores of four of G. bicolor compounds, 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and trans-5-p-coumaroylquinic acid when compared to the commercially available gliptin inhibitors; and (3) the computational investigation of DPPIV receptors in relation to protein-ligand binding.

The study demonstrated that 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and trans-5-p-coumaroylquinic acid compounds isolated from G. bicolor possess DPPIV inhibitory activity. These compounds are able to dock well to two of the DPPIV receptor active sites, S1 and S2. Molecular docking evaluation of G. bicolor compounds suggested 3-caffeoylquinic acid as a promising candidate with free-binding energy of −29.0750 KJ/mol, which is better than three of the commercially available gliptin drugs, sitagliptin, saxagliptin, and linagliptin. These data suggested the ability of 3-caffeoylquinic acid to dock well in inhibiting the action of the DPPIV receptor in the treatment of type-2 diabetes. Drug-likeness analysis supports the use of 3-caffeoylquinic as a drug lead compound. ADME properties can be taken as best-hit molecule and can be considered for further studies such as QSAR and molecular dynamics. Despite that, results obtained from this study require further validation of the inhibition action of G. bicolor compounds towards the DPPIV receptor using in vitro approach. The computational data supports the efficacy of G. bicolor compounds as naturally occurring DPPIV inhibitors and could be considered for development as a potent antidiabetic drug.

 

Source:

http://doi.org/10.1155/2017/5124165

 

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