α-Mangostin and its derivatives against estrogen receptor alpha

Abstract

Estrogen receptor alpha (ERα) acts as the transcription factor and the main therapeutic target against breast cancer. One of the compounds that has been shown to act as an ERα is α-mangostin. However, it still has weaknesses due to its low solubility and low potent activity. In this study, α-mangostin was modified by substituting –OH group at C6 using benzoyl derivatives through a step by step in silico study, namely pharmacokinetic prediction (https://preadmet.bmdrc.kr/adme/), pharmacophore modeling (LigandScout 4.1), molecular docking simulation (AutoDock 4.2), molecular dynamics simulation (AMBER 16) and a binding free energy analysis using MM–PBSA method. From the computational studies, three compounds which are derived from α-mangostin (AMB-1 (−9.84 kcal/mol), AMB-2 (−6.80 kcal/mol) and AMB-10 (−12.42 kcal/mol)) have lower binding free energy than α-mangostin (−1.77 kcal/mol), as evidenced by the binding free energy calculation using the MM–PBSA method. They can then be predicted to have potent activities as ERα antagonists.

Communicated by Ramaswamy H. Sarma

Keywords:

• α-Mangostin
• estrogen receptor alpha
• molecular dynamic
• pharmacophore modeling

Acknowledgements

We acknowledge the support of InteLigand Company for use of their facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We gratefully acknowledge the Rector of Universitas Padjadjaran and the Minister of Research and Higher Education for funding this project through the Grant of Dissertation Doctorate Research 2020 (PDD) from Ministry of Research and Technology/BRIN 1827/UN6.3.1/LT/2020 and Academic Leadership Grants 2020 No. 1427/UN6.3.1/LT/2020 from Universitas Padjadjaran.