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5-Nitroindazole against Lung Cancer: A multitargeted in-silico molecular docking and Molecular Dynamics simulation study
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1  Jamia Millia Islamia University
Academic Editor: Nicola Amodio (registering DOI)

Lung Cancer has taken over all cancers in terms of diagnosis and mortality worldwide, which is why it is on the World Health Organisation’s (WHO) priority list. As per the data reported by the WHO, cancer has caused 10 million death each year, and lung cancer alone caused 1.80 million deaths in 2020. Also, the FDA has approved almost 100 drugs against lung cancer, but it is not curable as most drugs target a single protein or block a single pathway. In this study, we screened the Drug Bank library against three major proteins- Ribosomal protein S6 kinase alpha-6, Cyclic-dependent protein kinase-2, and Insulin-like growth factor-1 of lung cancer- and identified the compound 5-Nitroindazole as a multitargeted inhibitor that potentially can treat lung cancer. For the screening, we deployed multisampling algorithms such as HTVS, SP and XP, followed by the MM\GBSA calculation, and the study was extended to molecular fingerprinting analysis, ADMET calculations and Molecular Dynamics simulation analysis to understand the complex’s stability. The docking scores against the proteins 6G77, 1AQ1 and 1K3A were -6.884 Kcal/mol, -7.515 Kcal/mol and -6.754 Kcal/mol, respectively, considered in a good scoring category. Also, the compound has shown all the values satisfying the ADMET criteria, and the fingerprint analysis has shown wide similarities. The molecular dynamics of each complex have shown a cumulative deviation of less than 2 Å, which is considered best for the biomolecules, especially for the protein-ligand complexes. The best feature of the proposed drug candidate is that it targets multiple proteins of lung cancer at the same time, the chance of developing resistance is relatively less, and it drastically can reduce the burden of the pharma industry.

Keywords: Lung Cancer; Molecular Docking; 5-Nitroindazole; Molecular Fingerprints; Molecular Dynamics Simulation.