Molecular simulations probing Kushecarpin A as a new lipoxygenase inhibitor.

Zizyphus oxyphylla Edgew is used in Pakistan as a folk medicinal remedy for inflammatory conditions, pains especially rheumatic pain, fevers, allergy and diabetes. The aim of the current study was to scientifically validate the folk use of Z. oxyphylla Edgew by using the isolated compound in vitro and in vivo levels. Kushecarpin A was isolated from ethyl acetate fraction of the plant crude extract. Molecular docking simulations predicted Kushecarpin A as a potential new lipoxygenase (LOX) inhibitor. Kushecarpin A showed significant lipoxygenase inhibition (IC(50): 7.2 ± 0.02 µM) thus validated computational prediction. It also exhibited significant and highly significant inhibition (p < 0.05 and p < 0.01) of carrageenan-induced hind paw oedema at the doses of 5, 10 and 20 mg/kg. Kushecarpin A seems to be a potentially new anti-inflammatory compound responsible for anti-inflammatory activities of Z. oxyphylla Edgew. In vitro and in vivo anti-inflammatory inflammatory activities were found in good agreement with the folk medicinal use of Z. oxyphylla Edgew in inflammatory disorders.

Molecular simulations of Taxawallin I inside classical taxol binding site of ß-tubulin.

A new taxoid Taxawallin I (1) along with two known taxoids (2-3) were isolated from methanolic bark extract of Taxus wallichiana Zucc. Structural characterization was confirmed by mass and NMR spectral techniques. Taxawallin I exhibited significant in-vitro anticancer activity against HepG2, A498, NCI-H226 and MDR 2780AD cancer lines. Tubulin binding assay was performed to assess its tubulin binding activity. Molecular docking analysis was performed to study the potential binding mode inside the taxol binding site of ß-tubulin.