Virtual screaning of anticancer efficacy of phloretin against apoptotic targets – An In Silico molecular docking study

Thangavelu Ranjanamala,Fatima Yousel Ghidan,Vanmathiselvi Krishanan,Casimeer C Sangeetha,Sundarajan Nagarajan Rajeswari,Alaa Yousef Ghidan,Ramanatha Shreemaya

doi:10.25081/jp.2021.v13.7268

Abstract

Recent advances demonstrate phytochemicals to be a potent anticancer therapeutic agent as various anti-cancer targets. This study depicts the anti-cancer potential against certain crucial common cancer targets leading to cancer cell proliferation and survival. The main objective of this study is to study the anti-cancer potential of phloretin against certain cancer targets. Ligand analysis was performed and Phloretin was chosen as the experimental ligand and Bcl-2, NF Kappa B, Carbonic anhydrase I (CA-1), Inducible Nitric Oxide Synthase (iNOS), Endothelial Nitric oxide synthase (eNOS), Caspase 3, and Caspase 9 proteins were chosen as targets. Induced fit molecular docking was performed by the use of Glide 6.5 software (Schrodinger - 2015). The docked poses were further evaluated based on binding energy, Conformational changes, and the amino acid residues involved in the protein-ligand interaction. The docking results depicted that phloretin showed notable binding affinity especially with carbonic anhydrase I, ENOS, and INOS. It also showcased significant potential against Caspase 3 and NF Kappa, thereby showing its potential as an effective anti-cancer therapeutics. During this study, the Inhibitory potential of Phloretin was studied as a result of this molecular docking study. This Insilico study revealed the binding efficiency of phloretin against the aforementioned targets. In vitro analysis is required for further validation of this data.

Highlights

Worldwide, cancer is the primary cause of death and it presents itself as a hindrance and leads to a significant decrease in life expectancy
Ligand analysis was performed and Phloretin was chosen as the experimental ligand and Bcl-2, NF Kappa B, Carbonic anhydrase I (CA-1), Inducible Nitric Oxide Synthase, Endothelial Nitric oxide synthase, Caspase 3, and Caspase 9 proteins were chosen as targets
The sitemap module of Schrodinger is another source to predict the binding sites of the protein.vIn this research study, the active site residues of Carbonic anhydrase 1, INOX, ENOX, Caspase 3, and Caspase 9 were predicted by Uniprot and Interpro scan web server

Summary

Introduction

Cancer is the primary cause of death and it presents itself as a hindrance and leads to a significant decrease in life expectancy. Regardless of recent advancements in the development of modern medicine, Cancer is still the root cause of mortality worldwide. The major treatment options for cancer are chemotherapy, radiotherapy, and surgery (Pratheeshkumar et al, 2015). There has been a constant development of novel anti-cancer drugs. The use of synthetic drugs hasn’t ameliorated the treatment efficiency and there has been no overall improvement in the survival rate of the patients (Choudhari et al, 2019). There is a need for the development of novel therapeutics for a safer and effective treatment approach

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