Virtual Inhibition Analysis of Bioactive Compound Brazilin (Caesalpinia sappan L.) Toward Progesterone Receptor or Lonaprisan in Breast Cancer Proliferation

Abstract

Breast cancer is one of the leading causes of death worldwide. The pathway of breast cancer in KEGG shows that the most effective pathway is through the progesterone receptor (PR). Brazilin is a bioactive compound of secang (Caesalpinia sappan L.) used to inhibit breast cancer through survivin and Bcl-2 pathway but the interaction with PR route is unknown. This research was conducted to determine the virtual interaction between brazilin and PR and its comparison with lonaprisan, so the potential of breast cancer drugs that can overcome through three targets at once with minimal side effects is expected to be known. There are five docking interactions, including the interaction of PRprogesterone, PR-brazilin, PR-brazilin-progesterone, PR-lonaprisan, and PRlonaprisan-progesterone. Protein and ligand preparation was performed by using Discovery Studio Client 2019 and PyRx 0.8, molecular docking was performed by using Hex 8.0.0 and visualization used Discovery Studio Client 2019. Virtual interaction results shows that lonaprisan has the most stable bond (lowest binding energy),-333.8kJ/mol but when progesterone was docked afterwards the result shows the opposite. Brazilin has a more stable bond compared to lonaprisan with a difference of 2.1kJ/mol and supported by hydrophobic bonds also capable of changing the position of progesterone in binding to PR so that it is estimated that brazilin has the potential as SPRMs, an alternative breast cancer drug to replace lonaprisan. Herbal medicine with brazilin can be estimated to fight breast cancer through 3 targets at once (survivin, Bcl-2, PR).

Etlingera elatior Compounds as Anticancer Agents of Breast Cancer Through Inhibition of Progesterone Receptor: An In Silico Study

“…The Lipinski rule of five was used in this study to assess the drug-like properties of compounds. The molecular weight, number of hydrogen donors and acceptors, solubility, permeability, level of GI absorption, and number of Lipinski violations were performed using SwissADME, a free online website tool (http://www.swissadme.ch/) (Daina, Michielin and Zoete, 2017). AdmetSAR was then utilized to evaluate the toxicity of the compounds (http:// lmmd.ecust.edu.cn/adm etsar2) (Yang, et al, 2019).…”