In silico and ADMET molecular analysis targeted to discover novel anti-inflammatory drug candidates as COX-2 inhibitors from specific metabolites of Diospyros batokana (Ebenaceae)

Diospyros batokana (Ebenaceae) is a valuable medicinal plant that grows in the wild in Zambia. The aqua crude plant extract is valuable in treating oxidative stress and microbes-related diseases. In this study, bioactive metabolites from the leaf of the plant were tentatively identified using ultra-high-pressure liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Raw LCMS data were processed using MZmine3.6. Pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, and isoarthonin, (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide were among the many metabolites identified from the plant studied using LCMS-MZmine 3.6. Furthermore, in silico anti-inflammatory molecular docking was applied to the five (5) metabolites with the aim of predicting the ability of the metabolites to inhibit the COX-2 enzyme. The docking simulation for the five metabolites was executed using the Auto-dock tools. The lowest binding energy of the complexes was visualized using Discovery Studio, 2021 Client l molecular viewer. Pyrenophorol, (N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl] −2,2-diphenylacetamide) and losartan were found to provide the lowest binding energy to COX-2 compared to the standard anti-inflammatory drug, diclofenac. Furthermore, binding affinities, inhibition constants, and ligand efficiencies demonstrated that pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, isoarthonin and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide could be useful as anti-inflammatory drug candidates supporting the traditional uses of D. batokana. However, the bioavailability radar and physicochemical properties only predict losartan, pyrenophorol, and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide to be bioavailable and suitable drug candidates. In silico and ADMET analysis, shows that the five metabolites could be used as anti-inflammatory drugs comparable to the standard drugs, diclofenac and ibuprofen. However, in vitro and in vivo studies are needed to further support our findings.