Structural insights and computational stability analysis of thiophene-derived inhibitors targeting human 5-lipoxygenase

Thiophene derivatives are showing wide biological applications; particularly, it exhibits potential binding affinity against Lipoxygenase enzymes. Therefore, the present study mainly focused to understand the structure, intermolecular interactions and conformational stability of the thiophene derivatives in the three different environments. Crystal structures of newly synthesized three thiophene derivatives were determined. In which, the structures I and II are almost planar and compound III is almost orthogonal to one another. Nevertheless, a density functional theory (DFT) study predicts planar conformation for the isolated molecules. All three crystal structures are stabilized by C‒H ··· O type of hydrogen bonding, C‒H ··· π and π ··· π stacking. Further, these three molecules are subjected to molecular docking and followed by molecular dynamics to understand the behaviour of the molecules in the active site environment. The article examines structure–activity relationships to identify the functional groups that contribute to potential therapeutic effects. It serves as a useful resource for scientists developing thiophene derivatives that are more effective and have fewer adverse effects.