Therapeutic Potential of HMF and Its Derivatives: a Computational Study

Abstract

Over the past century, chemicals and energy have increasingly been derived from non-renewable resources. The growing demand for essential chemicals and shrinking inventory make reliable, sustainable sources essential. Carbohydrates offer by far the greatest carbon supply. Furan compounds, a particular family of dehydration products, are believed to offer high chemical potential. Here, we analyze 5-HMF (5, hydroxymethylfurfural) and some of its derivatives in particular, a furan-type platform chemical. To analyze the therapeutic potential of HMF and its derivatives, this study utilized cutting-edge technologies such as computer-aided drug design, virtual screening, molecular docking, and molecular dynamic simulation. We conducted 189 docking simulations and examined some of the most promising dock poses using the molecular dynamic simulator. As for the receptors for our compounds, the leading candidates are human acetylcholinesterase, beta-lactamases, P. aeruginosa LasR, and S. aureus tyrosyl-tRNA synthetases. Out of all derivatives considered in this study, 2,5-furandicarboxylic acid (FCA) performed best.

Keywords: Antimicrobial; Docking; HMF; MD Simulation; Therapeutic.

Fig. 1

Two-dimensional plot of the interaction of compound FCA with the active site of acetylcholinesterase (4BDT)

Fig. 2

Two-dimensional plot of the interaction of compound FCA with the active site of β-Lactamase (1FR6)

Fig. 3

Two-dimensional plot of the interaction of compound FCA with the active site of LasR (2UVO)

Fig. 4

Two-dimensional plot of the interaction of compound FCA with the active site of Tyrosyl-tRNA synthetase (1JIJ)

Fig. 5

LasR (2UVO) and FCA complex MD simulation trajectories comprising root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuations (RMSF)

Fig. 6

Human acetylcholinesterase (AChE) (4BDT) and FCA complex MD simulation trajectories comprising root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuations (RMSF)

Fig. 7

Tyrosyl-tRNA synthetase (1JIJ) and FCA complex MD simulation trajectories comprising root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuations (RMSF)