Biotechnol Appl Biochem. 2020 Sep 24. doi: 10.1002/bab.2040. Online ahead of print.
Over the years, phytochemical compounds have shown compelling evidences in exhibiting powerful anti-tumor properties. Moreover, due to the lack of safety and high cost of cancer therapies, opportunities are being sought out in these compounds as an alternative treatment modality. Therefore in the present study, 1574 compounds from NPACT library was examined to excavate potent and non-toxic ALK inhibitors. Notably two pharmacophore hypotheses (AAAHP and DDRRR) were generated using ligand-based
and energy-based techniques respectively to eliminate false positive prediction in database screening. Further, molecular docking and Prime MM/GBSA analysis were performed on the screened compounds to examine inhibitory activity against ALK. The analysis revealed that the two hits, namely, NPACT00018 and NPACT01077, exhibited better docking scores, binding energies and also ensured excellent drug-likeness properties than the reference compound, Crizotinib. Finally, the results were subjected to molecular dynamics studies to gain insight into the stability of these compounds in the binding pocket of ALK Protein. Indeed, the useful predictions generated by the present computational models are of immense importance could further speed up the anti-cancer drug development in the near future. This article is protected by copyright. All rights reserved.