Structure assignment, conformational properties and discovery of potential targets of the Ugi cinnamic adduct NGI25

The structure assignment and conformational analysis of cinnamic derivative N-benzyl-N-(2-(cyclohexylamino)-2-oxoethyl) cinnamamide (NGI25) was carried out through Nuclear Magnetic Resonance (NMR) spectroscopy, Molecular Dynamics (MD) and Quantum Mechanics (QM), i.e. semiempirical and Density Functional Theory (DFT) calculations. Moreover, Homonuclear (COSY, NOESY) and heteronuclear (HSQC, HMBC) experiments were applied to assign its protons and carbons. After structure identification, NGI25 was subjected to computational calculations to reveal its most favorable conformations. In particular, MD studies were performed in two different solvents, DMSO of intermediate polarity and hydrophobic CHCl3. The obtained results suggest that NGI25 adopts similar conformations in both environments. In particular, the two aromatic rings of the molecule reside in spatial vicinity, while they remain quite distant from the cyclohexane. 2D NOESY experiments confirmed the in silico MD and QM calculations. Finally, molecular docking calculations were performed in order to reveal possible enzyme-targets for NGI25. Swiss target module was used to guide the discovery of new targets based on the structure of NGI. Indeed, it was predicted that NGI25 inhibited butyrylcholinesterase (BCHE) and lipoxygenase (LOX). Molecular docking experiments, followed by Molecular Dynamics studies, confirmed the favorable binding of NGI25 to both enzymes. Communicated by Ramaswamy H. Sarma

Automated summary

In this study, the structure assignment and conformational analysis of cinnamic derivative N-benzyl-N-(2-(cyclohexylamino)-2-oxoethyl) cinnamamide (NGI25) were conducted using various techniques such as Nuclear Magnetic Resonance spectroscopy, Molecular Dynamics, and Quantum Mechanics calculations. The results indicate that NGI25 adopts similar conformations in different solvents and exhibits potential inhibitory effects on butyrylcholinesterase and lipoxygenase enzymes.