Structural, computational and in silico studies of 4-bromo-3-flurobenzonitrile as anti-Alzheimer and anti-Parkinson agents

Abstract

A novel dimer of the 4-bromo-3-fluorobenzonitrile was crystallized and studied using a spectroscopic method such as the scanning electron microscope method. The computational simulations substantiated the structural analysis findings. The Hirshfeld surface analysis has been performed for visualizing, exploring and quantifying the intra and inter-molecular interactions that stabilize the crystal packing of the compound. The NBO and QTAIM analyses were applied to study the nature and origin of the attractive forces involved in the crystal structure. Further, the pharmacokinetic properties of the compound were evaluated, indicating good brain-blood barrier and central nervous system penetration capability. Hence, in silico studies was carried out to explore the binding pattern of the titled compound against acetylcholinesterase and butyrylcholinesterase, and tumor necrosis factor-alpha converting enzyme proteins using molecular docking and molecular dynamics simulations approach. Further, the titled compound is compared with standard drugs through molecular docking studies. The in silico studies finally predicts that the compound under investigation may act as a good inhibitor for treating Alzheimer’s disease and further in vitro and in vivo studies may provide its therapeutic potential.

Communicated by Ramaswamy H. Sarma

Keywords:

• Crystal structure
• DFT
• NCI
• molecular docking
• MMGBSA
• molecular dynamics simulation

Acknowledgments

The authors are thankful to the DST-FIST (SR/FST/PSI-119/2019), National Single Crystal Diffractometer Facility, DoS in Physics, CPEPA, IOE and DST-PURSE, Vijnana Bhavan, University of Mysore, Mysuru for providing the instrumentation facility and the authors thank Dr Tendamudzimu Tshiwawa, Department of Chemistry at Rhodes University, South Africa, and the center for High Performance Computing for having provided the computing (CHPC) resources used to carry out the simulation study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Vijayashree N. Hegde: Writing-Original Draft, Methodology, Data curation and software.

J. S. Shyambhargav: Writing-Original Draft, Methodology, Data curation and software.

B. S. Chethan: Conceptualization, Methodology, Software, validation and Formal analysis.

Mofeli Benedict Leoma: Software, Molecular dynamics simulation.

N. K. Lokanath : Resources, Writing-Review and Editing, Software, Visualization, Supervision, Project administration.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.