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.

Variation of heavy metal contamination between mushroom species in the Copperbelt province, Zambia: are the people at risk?

BACKGROUND: Heavy metal contamination in mushrooms and the associated health risk are unknown in Zambia. We studied seven heavy metals and 23 mushroom species and interviewed 400 people. RESULTS: Mushrooms were found to contain substantial concentrations of Cu (894.4 ± 267.9 µg g-1 ) and Fe (998.4 ± 454.0 µg g-1 ). Significant differences in transfer factors of metals occurred between mushroom species (F11,66  = 5.36, P < 0.001). The most efficient were L. kabansus (for Zn and Ni), A. miomboensis (for Cu and Fe) and T. clypeatus (for Mn, Pb and Co). These species were also among the most preferred mushrooms for consumption based on the interviews conducted. Although 60% of the mushrooms observed were edible, only 20% were frequently consumed during the mushroom season. High positive correlations observed between soils and mushrooms suggest that contamination in mushrooms increases with soil pollution. The estimated daily intake of metals and the target hazard quotient through mushroom consumption were found to be significantly influenced by mushroom species (F11,66  = 38.8, P < 0.001) suggesting that the level of exposure to heavy metals depends on the species of mushroom consumed. CONCLUSIONS: The study has revealed that heavy metal concentrations in mushrooms exceed permissible limits and vary between species. Transfer efficiency also varies between mushroom species and contamination in mushrooms increases with soil pollution. The fact that concentrations of metals in soil were significantly high, the risk of exposure through mushroom consumption and possibly soil ingestion is even higher. © 2019 Society of Chemical Industry.

Assessment of Heavy-Metal Pollution in Sediments and Tilapia Fish Species in Kafue River of Zambia.

We report results from an evaluation of the levels of heavy metals, i.e., copper (Cu), cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), chromium (Cr), and iron (Fe) in sediment and tilapia fish samples from a wide stretch of the Kafue river of Zambia. In sediment samples, the highest Pb and Fe concentrations were recorded at Hippo Dam, i.e., 36.2 ± 0.1 mg/kg dw and 733 ± 37 mg/kg dw at Kafue Town, respectively. Other notably high metal concentrations in sediment were Cr at Kafue Bridge (42.5 ± 0.1 mg/kg dw [dw]), Cu at Mpongwe (233 ± 5 mg/kg dw), and Mn at Kafue Town (133 ± 1 mg/kg dw); it was highest at Ithezi Tezhi Dam at 166 ± 1 mg/kg d. Three fish species, i.e., three-spot bream Tilapia andersonii, red-breasted bream T. rendalli, and nile tilapia Oreochromis niloticus were evaluated for levels of the seven metals. The concentrations of the metals in these fish species afforded estimation of the biota sediment-accumulation factor, which is the ratio of the concentration of the metal in liver to that in the sediment. The coefficients of condition (K) values, which give an indication of the health of the fish, were also estimated. The K values ranged from 2.5 ± 0.5 to 5.1 ± 0.6 in all of the three fish species. Partial least squares analysis showed that heavy metals are generally sequestered evenly in all of the parts of all of the three fish species except for elevated levels of Mn, Cd, and Pb in the liver samples.