Understanding the impact of anticancer halogenated inhibitors and various functional groups (X = Cl, F, CF3, CH3, NH2, OH, H) of casein kinase 2 (CK2)

Abstract

Main focus of study is to understand potency of halogen (X = Br) atom that exists in tetrabromobenzotriazole (TBB) derivatives of crystal CK2 ligand along with hinge region amino acids (VAL45, PHE113, GLU114, VAL116, ASN118) through interaction energy analysis. In turn to attain profound insight on nature of stabilization of core CK2 ligands: 1ZOE-L1, 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 2OXY-L5, 3KXG-L6, 3KXH-L7 -L7 and 3KXM-L8, having four bromine atoms, we attempted to mutate all bromine (X = Br) atoms by various functional groups (X = Cl, F, CF3, CH3, NH2, OH, H) and binding strength along with amino acids was calculated. Most stable ligands exist in mutated NH2 functional groups: 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 3KXM-L8 having interaction energy as −5.21, −14.87, −6.69 and −11.72 kcal/mol respectively, revealing strong binding strength. Second most stable mutated Cl functional group ligands also play a major role in 1ZOH-L3, 2OXX-L4 and 3KXM-L8 having interaction energy as −6.89, −5.37, and −10.48 kcal/mol respectively. Overall, this study will pave way for crystal growth and medicinal chemist to have cleared perceptive about structural properties of CK2 halogenated ligands with new insight on CK2 mutated functional group ligands. Further, it insists us to reuse existing CK2 crystal ligand with more preferable suggested binding contacts in course of new functional groups that lead to anticancer affinity. Communicated by Ramaswamy H. Sarma