Homo Sapien Bcr-Abl-Interacting Scaffolds from Bryophyllum pinnatum and Cantharanthus roseus: Computational Studies

Abstract

Leukaemia is one of the ten life-threatening cancer of the world today. Chronic myelogenous leukaemia (CML), in particular constitutes about 15% of adult leukaemia and is characterised by over-production of immature myeloid cells in the bone marrow, spleen and peripheral blood resulting in the presence of the constitutively activated tyrosine kinase BCR-ABL, the cardinal therapeutic target. With the prevailing patients resistant to current drugs, it is imperative to come up with novel drugs particularly of plant origin considering the critical roles natural products (plants) play in the discovery and developments of new pharmaceuticals. In the present study, Virtual High Throughput Screening of phytochemicals from Bryophyllum pinnatum and Cantharanthus roseus (reported anticancer plants) against the Bcr-Abl catalytic site for possible drug scaffolds were carried out. A library of phytochemical compounds (ligands) was generated and multiple docking of the ligands against the Bcr-Abl catalytic site was executed with the Autodock Vina algorithm. Docking scores from Autodock vina were validated via the online available ChembL database and a correlation coefficient of 0.7 was obtained from a plot of the docking scores of 43 compounds from ChembL database with their corresponding pIC50 values. The lead compounds from Virtual High Throughput Screening, Cynaroside and Rutin have a binding energies of -9.6 kcal/mol and -9.4 kcal/mol respectively when compared with the co-crystallized nilotinib’s -9.4 kcal/mol. Pharmacological kinetics analysis indicated that Cynaroside, with a bit of optimization could end up a potential anti-CML drug.