Drug Design based on vouacapanic derivative with antileukemic activity

Leukemia is a neoplasm of hematopoietic tissue originating from the bone marrow and can be classified according to the cell line involved as myeloid and lymphoid. The studies have evidenced the essential role of the control of BCR-ABL tyrosine kinase activity for the treatment of chronic myelogenous leukemia (COWAN-JACOB et al., 2007). The main objective of this work is drug design that act as inhibitors of ABL tyrosine kinase activity, responsible for the proliferation of these tumor cells. Among the naturally occurring compounds with activity in K562 chronic myeloid leukemia tumor cells, the vouacapanic derivative 16-(N,N-Diethylamino)methylene-6α-hydroxivouacapan-7β,17β-lactone has such proven biological activity (EUZEBIO et al., 2010). Virtual screening was performed to obtain similar structures from the vouacapanic derivative with potential activity in the K562 cells. The structures obtained by virtual screening were submitted to studies of predictions of pharmacokinetic and toxicological properties, as well as, molecular docking study with the BCR-ABL tyrosine kinase receptor, extracted from the protein databank (PDB ID 1IEP) to predict the binding affinity between the protein-ligand complexes. A compound which showed the better binding affinity was ZINC38664626, has had good pharmacokinetic and toxicological parameters, showing to be a promising compound to be used as a drug.