In silico targeting breast cancer biomarkers by applying rambutan (Nephelium lappaceum) phytocompounds

Abstract

Worldwide, breast cancer is the leading type of cancer among women. Overexpression of various prognostic indicators, including nuclear receptors, is linked to breast cancer features. To date, no effective drug has been discovered to block the proliferation of breast cancer cells. This study has been designed to discover target-based small molecular-like natural drug candidates that have anti-cancer potential without causing any serious side effects. A comprehensive substrate-based drug design was carried out to discover the potential plant compounds against the target breast cancer biomarkers including phytochemicals screening, active site identification, molecular docking, pharmacokinetic (PK) properties prediction, toxicity prediction, and molecular dynamics (MD) simulation approaches. Twenty plant compounds extracted from the rambutan (Nephelium lappaceum) were obtained from PubChem Database; and screened against the breast cancer biomarkers including estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR). The best docking interaction was chosen based on the higher binding affinity. Analyzing the pharmacokinetic properties and toxicity prediction results indicated that the fifteen selected plant compounds have good potency without toxicity and are safe for humans. Four phytochemicals with a higher binding affinity were chosen for each breast cancer biomarker to study their stability in interaction with the target proteins using MD simulation. Among the above compounds, Ellagic acid showed the high binding affinity against all three breast cancer biomarkers.

Communicated by Ramaswamy H. Sarma

Keywords:

• Breast cancer
• virtual screening
• pharmacokinetics
• ADME
• MD simulation

Acknowledgment

The authors like to acknowledge the Research Center for Pharmaceutical Nanotechnology at Tabriz University of Medical Sciences for their technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes

1 www.swissadme.ch

2 http://lmmd.ecust.edu.cn/admetsar2/

Additional information

Funding

This study was supported by the Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences (#70374).