Efficacy of Phytochemicals of Cassia Angustifolia in Chronic Myeloid Leukaemia – An In-silico Analysis

Abstract

Objective: To discover the compounds of Cassia having activity against the BCR-ABL fusion protein involved in the pathogenesis of CML and to compare it with previously developed inhibitor, nilotinib using in-silico molecular docking.

Methodology: The 3D structure of Human BCR-ABL fusion protein was obtained from PDB (RSCB). The SMILES and Chemical Structures of the ligands were obtained from PubChem. They were prepared in Mol SDF format by the Chem Bio Draw and then converted to PDBQT format using PyRx tool for generating the atomic coordinates for molecular docking.  Molecular docking of Nilotinib, Quercimeritin, and Scutellarein with Human ABL Kinase was performed using Autodock4. The ADMET properties were described using Swiss ADME, a web-based tool.

Results: All the three compounds under study bind and make stable complexes with wild-type BCR ABL with the global energies of -12.46, -16.17kCal/mol and -15.41kCal/mol for Nilotinib Scutellarein and Quercimeritin respectively which means that these compounds can act as selective inhibitors of BCR-ABL fusion protein. Quercimeritin, also form Hydrogen bonds with GLU 286 and Asp 381,

Conclusion: The binding energies of the phytochemicals of Cassia are higher in comparison with Nilotinib which has a binding energy of -12.46kCal/mol which suggests a better inhibitory potential of these compounds. Quercimeritin also forms Hydrogen bonds with Glutamine 286 and Aspartate 381, hence its potential to be a potent inhibitor of the BCR- ABL fusion protein is more promising Nilotinib. Further in vitro and in vivo studies are suggested to elaborate the anti-neoplastic potential of Quercimeritin in CML.