Computational Investigation of Indazole Scaffolds as Tyrosine Kinase Inhibitors Using Molecular Docking and ADMET Prediction

Anuruddha Rajaram Chabukswar*, Rajesh Bibhishan Nanaware, Prajakta V. Adsule and Swati C Jagdale

Department of Pharmaceutical Chemistry, School of Pharmacy, Dr. Vishwanath Karad MIT-World Peace University, Pune, Maharashtra, India.

Corresponding Author E-mail: anuruddha.chabukswar@mitwpu.edu.in

DOI : http://dx.doi.org/10.13005/bbra/3013

ABSTRACT:

Non-small-cell lung cancer accounted for approximately 85% of newly diagnosed lung cancer cases. In non-small cell lung cancer and tuberculosis, level of vascular endothelial growth factor was found to be elevated; which induces angiogenesis. Many inhibitors are approved for the treatment of non-small cell lung cancer and tuberculosis. However, resistance and severe side effects trigger the search for novel and more potent anti-cancer as well as anti-tuberculosis agents. In this study, molecular docking analysis along with pharmacokinetic ADMET and drug likeness prediction were carried out to evaluate the newly designed indazole scaffolds as potent tyrosine kinase VEGFR-inhibitor. These scaffolds exhibited better binding affinity and favorable interactions with VEGFR-2 enzymes (PDB ID: 4AGD and 4AG8). Out of 10 screened compounds, three most potent compounds (SMO, SBS and SOT) having good scores against 4AGD (-6.99, -6.96 and -6.88 kcal/mol) and compounds (SS, SSA and SMO) having significant scores against 4AG8 (-7.39, -6.71 and -6.70 kcal/mol) emerged as effective and potent VEGFR-2 inhibitors. Based on drug-likeness for oral bioavailability and ADMET risk parameters all the indazole scaffolds may exhibit significant activity. The findings from these current as well as future research efforts will clarify the role of newer indazole derivatives against non-small cell lung cancer and tuberculosis.

KEYWORDS: Dug-likeness; Indazole; Molecular Docking; Vascular Endothelial Growth Factor Receptors

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