Structure-Based Virtual Screening of Eugenol Against CTNNB1, Ep300, and CD44

 Structure-Based Virtual Screening of Eugenol Against CTNNB1, Ep300, and CD44

Preema Karal Andrade1, Manjunatha Hanumanthappa *2

1Department of PG Studies and Research in Biotechnology & Bioinformatics, Kuvempu University, Shankaraghatta, Karnataka, INDIA;

2Department of PG Studies and Research in Biochemistry, Jnana Bharathi, Bangalore University, Bangalore, Karnataka, INDIA.

Running title: Structure-Based Virtual Screening of Eugenol

Correspondence:

Manjunatha Hanumanthappa

Department of PG Studies and Research in Biochemistry,

Jnana Bharathi, Bangalore University,

Bangalore-560 056, Karnataka, INDIA.

E-mail ID: manjunatha75@gmail.com

ABSTRACT

Eugenol is a natural component obtained mainly from cloves. It is proven that eugenol has an anticancer and anti-oxidant properties in many cancers. Eugenol can also inhibit the expression of β-catenin in breast and lung cancer. CTNNB1 is a gene that encodes β-catenin which is the intracellular scaffold protein and a crucial component in the Wnt signaling pathway and responsible for carcinogenesis of various types of cancer. EP300/p300 is found to be a nuclear transcriptional regulator of Wnt signaling and CD44 is a β-catenin target gene. Structure-based virtual screening has been used in the early stage of drug discovery to discover small ligand molecules. The study aims to predict the binding mode of eugenol as a ligand with known three-dimensional structure of CTNNB1, EP300, and CD44. AutoDock Vina was utilized to perform molecular docking analysis of the ligand-receptor complexes. Ligand-binding affinity was predicted by computing negative Gibbs free energy (-∆G) using AutoDock Vina scoring function (Kcal/mol). This study revealed the significant binding energy between eugenol-CTNNB1, eugenol-EP300, eugenol-CD44, and the standard erlotinib-CTNNB1, erlotinib-EP300, and erlotinib-CD44 complexes.

Key words: Eugenol, β-catenin, Wnt signaling, Molecular docking, AutoDock Vina