486994-24-5Relevant articles and documents
Design, synthesis, biological evaluation, and molecular modeling studies of rhodanine derivatives as pancreatic lipase inhibitors
Chauhan, Divya,George, Ginson,Sridhar,Bhatia, Rohit,Paul, Atish T.,Monga, Vikramdeep
, (2019)
A series of rhodanine-3-acetic acid derivatives were synthesized via Knoevenagel condensation of rhodanine-3-acetic acid with various substituted aromatic aldehydes. The synthesized derivatives were screened in vitro for understanding the inhibitory potential towards pancreatic lipase (PL), a key enzyme responsible for the digestion of dietary fats. Derivative 8f exhibited a potential inhibitory activity towards PL (IC50=5.16 μM), comparable to that of the standard drug, orlistat (0.99 μM). An increase in the density of the aromatic ring resulted in potential PL inhibition. The enzyme kinetics of 8f exhibited a reversible competitive-type inhibition, similar to that of orlistat. Derivative 8f exhibited a MolDock score of -125.19 kcal/mol in docking studies, and the results were in accordance with their PL inhibitory potential. Furthermore, the reactive carbonyl group of 8f existed at a distance adjacent to Ser152 (≈3 ?) similar to that of orlistat. Molecular dynamics simulation (10 ns) of the 8f-PL complex revealed a stable binding conformation of 8f in the active site of PL (maximum root mean square displacement of ≈2.25 ?). The present study identified novel rhodanine-3-acetic acid derivatives with promising PL inhibitory potential, and further lead optimization might result in potent PL inhibitors.
