Open AccessMolecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer
Author(s) -
Doni Dermawan,
Riyadi Sumirtanurdin,
Deti Dewantisari
Publication year - 2019
Publication title -
ijpst (indonesian journal pharmaceutival science and technology)/ijpst (indonesian journal of pharmaceutical science and technology)
Language(s) - English
Resource type - Journals
eISSN - 2406-856X
pISSN - 2356-1971
DOI - 10.24198/ijpst.v6i2.18168
Subject(s) - andrographolide , pharmacophore , breast cancer , tamoxifen , estrogen receptor , andrographis paniculata , molecular dynamics , estrogen receptor alpha , medicine , chemistry , cancer , pharmacology , stereochemistry , computational chemistry , alternative medicine , pathology
Breast cancer is the most common cancer suffered by women with 1.67 million new cases in the world by 2012 with a mortality rate of 12.9%. Tamoxifen is a standard therapy for breast cancer but can cause endometrial and thromboembolic cancer. Andrografolid is an active compound from Andrographis paniculata which has antiproliferation activity of MCF-7 breast cancer cells with IC50 was 61.11 μM. The purpose of this study was to design andrographolide modification structures as human estrogen receptor alpha (hER-α) antagonists. Molecular docking simulation results showed that the andrographolide and AND5 (best andrographolide derivative) have free binding energy (ΔG) values were -9.65 kcal/mol and -12.43 kcal/mol, respectively, and hydrogen bonds were formed with Gly521, Asp351, and Met343. The ΔG value of ANDS was lower than tamoxifen (-11.40 kcal/mol). Pharmacophore modeling results showed that andrographolide and AND5 had a high pharmacophore-fit value of 46.39% and 63.47%, respectively. Molecular dynamics simulation using MM-PBSA calculation method, showed that the hERα-AND5 system has a value of ΔGTOTAL = -50.52 kcal/mol compared to the hERα-estradiol system as an agonist with a value of ∆GTOTAL = -40.86 kcal/mol . These results suggested that AND5 has better affinity for hERα compared to estradiol so that AND5 is a very promising anti breast cancer agent.Keywords: Andrographolide, molecular dynamics, breast cancer, molecular docking, estrogen receptor alpha