Theoretical Investigation of Some Substituted N-Phenylacetamides as Potential Inhibitors of the Biotin Carboxylase Enzyme: Thermodynamic Functions, Global Reactivity Descriptors and Molecular Docking Assessment

In the current work, the amine derivatives were evaluated with two computational programs with a total of six compounds. The former was Gaussian, which allowed the calculation of thermodynamic functions (ΔG, ΔH, and ΔS), chemical hardness (η), chemical potential (μ) and global electrophilicity index (ω). AutoDock Vina was the second program used, which was employed in molecular docking studies. Biotin Carboxylase (BC) (PDB ID: 3JZF), was chosen  as the target  protein. BC is a crucial part of the acetyl-CoA carboxylase (ACC) complex, which plays a vital role in bacterial fatty acid biosynthesis, by converting acetyl-CoA to malonyl-CoA, an intermediate product. This enzyme inhibitor can be used to inhibit the growth and proliferation of bacteria.

The purpose of this research is to use molecular docking with AutoDock Vina to see if the studied compounds could bind to the active site of Biotin Carboxylase (BC) (PDB ID: 3JZF). Compounds S2 and S5 were the most promising compounds with the predicted binding affinity of −6.2 kcal/mol and S6 predicted binding affinity of −5.8 kcal/mol, respectively.

In addition to π–π, π–alkyl, π–σ, cation–π, and van der Waals interactions, the results indicated the formation of hydrogen bonding between GLY165, GLY166, LYS159, HIS236, TYR82 and ASP382. The CF3 group in compound S6 was involved in three hydrogen-bond interactions. In this study S2, S5, and S6 were the most promising compounds for enzyme inhibition. The predicted binding affinities of compounds S2 and S5 were found to be the most favorable and they also had the highest value in calculated thermodynamic parameters. The highest values were obtained for compound S5, with ΔG = 0.206713, ΔH = 0.266856, and ΔS = 126.583. This was followed by compound S2, with thermodynamic function values of ΔG = 0.178726, ΔH = 0.231667, and ΔS = 111.424. The results obtained by Gaussian and the results obtained by AutoDock Vina are seen to be correlated consistently with this result.