Probing the intermolecular interactions, binding affinity, charge density distribution of N-(3-chlorophenyl)-2-cyanoacetamide (NCPC) against Alzheimer’s disease: Insights of experimental and computational techniques

The increase in the findings of the novel methodologies has contributed to the development of the new compounds with enhanced properties. The exploration of the different properties experimentally is an expensive and resource-intensive procedure. Hence, the use of the computational tools to find and validate the various properties will help in the failures of the newly synthesized compounds with drug related properties. In this regard, we report the synthesis of N-(3-chlorophenyl)-2-cyanoacetamide (NCPC) compound and its investigation as therapeutic agent to target the Alzheimer’s disease (AD) with inhibitory potential evaluated against cholinesterase (ChE). The Hirshfeld Surface Analysis (HSA) revealed the various intra- and intermolecular interactions involved in the crystalline environment, and they are found to be in corroboration with the obtained X-ray diffraction (XRD) results. Further, to explore the role of non-covalent interactions toward the binding affinity of the compound Quantum Theory of Atoms In Molecule (QTAIM) analysis was employed. Natural bond orbital analysis was performed to examine the intramolecular hyperconjugations and charge delocalization in the molecule. In silico Structure Activity Relationship (SAR) study was carried out through molecular docking and its binding score is found to be −6.00 kcal/mol. Further, the molecular dynamics study revealed a good binding affinity between the protein and the ligand. Molecular dynamics simulations determined the stability and binding modes of the NCPC compound with the most inhibition efficiency for the reversible of the AD. According to our findings, the NCPC molecule offers useful templates to develop novel multipurpose drugs that can be used to treat AD.