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- Title
In-silico Screening of Selected Flavanone Compounds for HMG Co-A Reductase Inhibitory Activity.
- Authors
Ying, Tan Ker; Shukkoor, Mohamed Saleem Abdul; Khalivulla, Shaik Ibrahim
- Abstract
Hypercholesterolemia is one of the potential modifiable risk factors for cardiovascular diseases, the main leading causes of death globally. To keep serum levels of total cholesterol and LDL within the normal limit, statins (HMG CoA reductase inhibitors) are widely prescribed. Statins are generally well tolerated, yet recent studies reported that the use of statins could lead to adverse effects such as elevated hepatic transaminases level, myalgia, and increased risk of diabetes. These adverse effects could reduce patient compliance and results in poor therapeutic outcomes. Various flavanones are shown to possess anti-hypercholesterolemia effect in vitro, in silico and in vivo. The objectives of this study were to estimate the binding energies of the selected flavanone compounds against HMG CoA reductase through in-silico screening and to determine the structural activity relationship (SAR) of the selected flavanone compounds in silico. The selected flavanones are eriocitrin, eriodictyol, hesperitin, hesperidin, neohesperidin, naringin, naringenin and narirutin. Atorvastatin was used as a positive control to validate the binding and to compare the binding energies of the selected flavanones. The structure of the human HMG CoA reductase (PDB ID: 1DQA) was downloaded from Protein Data Bank, whereas the structures of the flavanones were downloaded from ZINC database. All the compounds were prepared using AutoDock Tools 1.5.6. Then, they were docked against the human HMG CoA reductase using AutoDock Vina 1.1.2 and Accelrys Discovery Studio 4.5. The interactions between flavanones and the protein were analyzed and their structure-activityrelationships were also determined. Results: The binding energy of atorvastatin as a control was -8.0 kcal/mol. Eriocitrin (-10.0 kcal/mol), hesperidin (-9.7 kcal/mol), neohesperidin (-9.5 kcal/mol),narirutin (-9.5 kcal/mol) and naringin (-9.1 kcal/mol) exhibited greater binding affinity towardsHMG CoA reductase, as compared to atorvastatin. They are flavanone glycosides. The aglyconeflavanone compounds, eriodictyol (-7.4 kcal/mol), hesperitin (- 7.6 kcal/mol) and naringenin (-7.4kcal/mol) exhibited lower binding energy than atorvastatin. However, they have total polarsurface area (TPSA) lower than 140 ?2 and do not violate the Lipinski's Rule of Five. Discussionand Conclusion: There are studies which showed that the aglycone flavanones (eriodictyol, hesperitin, and naringenin) possess HMG Co-A reductase inhibitory activity. With theircomparable binding energies shown in this study, the eriodictyol, hesperitin and naringenin aresuitable to be used for future drug development against dyslipidemia.
- Subjects
HESPERIDIN; NARINGIN; BINDING energy; DISEASE risk factors; FLAVANONES; PATIENT compliance; REDUCTASE inhibitors
- Publication
Current Trends in Biotechnology & Pharmacy, 2020, p105
- ISSN
0973-8916
- Publication type
Article