TARGETING NUCLEAR FACTOR KAPPA B WITH CHELATED ZINC COMPOUNDS TOWARDS ANTICANCER DRUG DESIGN

Inbathamizh L,Srinivasan P T,Nagalakshmi K,Shila S,Thenmozhi A,Rasappan P

doi:10.22159/ijap.2021v13i4.41650

Abstract

Objective: The objective of the study was to analyse the target-ligand interactions between nuclear factor-κB (NF-κB) and chelated Zinc compounds and to explore the anticancer drug potential of these ligands by a bio computational approach. Methods: Bioinformatics databases and tools were applied for the study. Three dimensional structure of the target NF-κB was retrieved from Protein Data Bank (PDB). The optimized structures of two chelated Zinc compounds, Zinc acetate and Zinc orotate were taken for docking studies with the target using docking tool AutoDock 4.2. Drug properties of the ligands were further assessed by Molinspiration server. Results: Docking results as predicted by AutoDock and as visualized by PyMol viewer were effective for both the ligands. Comparatively, Zinc orotate showed minimum energy and more interactions with the target. Both the ligands satisfied the Lipinski’s rule of five with zero violations. Conclusion: The findings emphasized the promising role of chelated Zinc compounds as potent drug candidates in anti-cancer drug design against NF-κB.

Highlights

Nuclear factor-κB (NF-κB) is an important protein regulating gene expressions involved in various cellular processes
Two chelated Zinc compounds namely Zinc acetate and Zinc orotate with the Zinc metal chelated to organic ligands were chosen as the ligands for docking with the target NF-κB
The crystal structure of the target protein human NF-κB was retrieved from Protein Data Bank (PDB) with ID 1SVC as shown in fig

Summary

Introduction

Nuclear factor-κB (NF-κB) is an important protein regulating gene expressions involved in various cellular processes. It has a major role in cell proliferation, growth of tumors, metastasis, and angiogenesis contributing significantly to cancer initiation and progression [1,2,3,4]. It is a family of five transcription factors which are NF-κB1/p105, NF-κB2/p100, RelA/p65, RelB, and c-Rel [5]. Tumor regression with NF-κB suppression observed in earlier studies indicates the promising role of NF-κB as a therapeutic target in anticancer studies [8,9,10]

Methods

Results

Conclusion