Computational screening for the identification of potent tubulin inhibitors as anticancer agents

Abstract

Tubulin is a biological target for several multiple clinically used anticancer drugs which is responsible for chromosome segregation, cell shape maintenance, transport, motility, and organelle dispersion, among other things. For decades, anticancer medicines that target the microtubule, such as taxanes and vinca alkaloids, have formed the cornerstone of many chemotherapy regimens. However, these medicines have substantial drawbacks, prompting the development of new microtubule targeting compounds. The pyrazole ring system is a critical component of various tubulin inhibitors discovered in recent years. In the present study, a dataset of tubulin inhibitors have been downloaded from PubMed database and included for screening study by Glide module. The Lipinski rule of 5, high-throughput virtual screening, standard precision, and extra precision methodologies have been used for final screening of potent compounds against tubulin protein (PDB ID: 3E22). The docking studies of these inhibitors revealed a complementary fit in the allosteric site of Tubulin protein. Among all the selected inhibitors, Centaureldin and Chalcones MDL showed the highest docking scores of −7.76 and −6.21 kcal/mol, respectively, when compared with the cocrystal ligands of PDB-3E22. Postmolecular mechanics/generalized born surface area analysis of these potent inhibitors showed dG binding values −37.83 and −28.37 kcal/mol, respectively. On the basis of final screened compounds, we can further develop pharmacophore model and screened potential compounds against tubulin protein.