Demethoxylated curcuminoids as antidiabetic complication drug leads – in silicostudies

Abstract

Curcuma longa is used traditionally in the treatment of diabetes and diabetic complications. Aldose Reductase (ALR2) inhibition is a plausible therapeutic strategy against diabetic complications. This work was aimed at evaluating Curcuma longa phytochemicals, in silico, for their ALR2 inhibitory potentials. Thirty-nine (39) phytoconstituents of Curcuma longa were subjected to a succession of in silico screenings comprising molecular docking, drug-likeness and safety profiling to identify ALR2 inhibitor leads, validating their binding interactions with molecular dynamics simulations at 50 ns simulation time. The in silico evaluations afforded two demethoxylated curcuminoids, bisdemethoxycurcumin and demethoxycurcumin, as potential ALR2 inhibitor leads forming stable ALR2 complexes, their relative potencies correlating to their degrees of demethoxylation. The two curcuminoids are herein recommended as leads for the discovery of ALR2 inhibitory antidiabetic complication drug leads.

Keywords

• In silico drug discovery, Aldose reductase inhibition, Curcuma longa, Curcuminoids, Diabetic complication