Molecular docking analysis of flupenthixol and desmethylastemizole with the apoptotic regulator proteins CFLAR and TRAF2 linked to lung carcinoma.

Subrata Das

doi:10.6026/97320630017470

Abstract

It is known that molecular changes in apoptotic genes due to mutation may cause disruption of apoptotic pathway resulting in an abrupt increase in cell proliferation. Therefore, it is of interest to identify compounds that could potentially replenish the changes in the apoptotic pathway, resulted from mutation. The gene network analysis using the Network Analyzer Plugin of Cytoscape (3.5.1) shows CFLAR and TRAF2 as influential genes in the apoptotic pathway. Mutation in these genes brings loss in apoptotic property of a cell and thus increases the cell proliferating activity. Thus, data on the molecular docking analysis of four natural compounds from Ottelia alismoides (L.) Pers with the two target proteins were reported. Flupenthixol and desmethylastemizole was found to be two efficient ligand molecules based on ligand-target interaction. In stereochemical quality assessment, the Ramachandran plot analysis of receptors indicates the better stereochemical characteristics for receptor-ligand interaction.

Highlights

Cancer is one of the deadliest complications worldwide
It is of interest to document the molecular docking analysis data of Flupenthixol and desmethylastemizole with the apoptotic regulator proteins CFLAR and TRAF2 linked to lung carcinoma [4] for consideration in drug discovery
At that condition ligand molecule binding with the TRAF2 (Figure 1) and CFLAR (Figure2) can block their activity to minimize their gain of proliferating nature

Summary

Introduction

Cancer is one of the deadliest complications worldwide. Based on the latest report of World Health Organization (WHO), approximately 9.6 million deaths occurred globally in 2018 is due to cancer and is estimated to rise to 20 million new cases by 2025 [1]. Lung cancer is more than one-fourth of deaths worldwide. Sixty percent of lung cancer patients are diagnosed at late stages with metastasis, where cell proliferate very quickly, and chances of survival become very minimal. Identification of novel therapeutic targets and lead molecule against lung cancer proliferation and metastasis are urgently essential to enhance patients’ survival [2]. Apoptosis has been known to play a vital role in the maintenance of tissue homeostasis by selective eradication of unwanted cells. Network pharmacology is a modern subject of interest based on the features of biological molecules. It provides an insight into multiple influential databases, which allows us to understand the underlying mechanisms of medicine and diseases. It is of interest to document the molecular docking analysis data of Flupenthixol and desmethylastemizole with the apoptotic regulator proteins CFLAR and TRAF2 linked to lung carcinoma [4] for consideration in drug discovery

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Results

Conclusion