In Silico study of Rosmarinic Acid Derivatives as Novel Insulin Fibril Inhibitors
The self-assembly of human insulin (HI) plays a crucial role in regulating amyloid fibrils. Therefore, it is a significant problem for the medical management of diabetes therapy and these findings have led us to investigate the amyloid formation and its inhibition. Few potential inhibitors have been identified to inhibit amyloid fibrils. Rosmarinic acid (RA) is one of the things that inhibits amyloid formation completely by increasing the resistivity of the amyloidogenic insulin (dimer) protein to thermal unfolding. Here, we choose different tested derivative compounds for designing amyloid inhibitors by substituting various functional groups of RA. These derivative compounds were subjected to in silico studies to determine the best drug candidates. In comparison to RA, 14 molecules have higher binding affinity and interactions with the target receptor. After frontier molecular orbitals study, ADME and toxicity analysis, the eight best compounds may act as the best inhibitors. The stability of the docked complexes was visualized by molecular dynamics (MD) simulations. This finding opens a new proposal to explore future studies with these best compounds to increase the thermal stability of the insulin dimers.