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

Keywords:

• CK2
• Interaction energy
• frontier molecular orbital’s
• polarizability
• volume
• and molecular mass

Acknowledgements

The author expresses her sincere thanks to B. Vijaya Pandiyan, Post-Doctoral Fellow, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology (IIT) Madras, India for few computational facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was part of the Research Project (File Number: YSS/2015/000275) and Palanisamy Deepa, is thankful to Science and Engineering Research Board (SERB), Government of India, New Delhi for the award of the Project and financial assistance.