Computer-aided identification of natural lead compounds as cyclooxygenase-2 inhibitors using virtual screening and molecular dynamic simulation.

In order to find more natural lead-compounds as inhibitors for Cyclooxygenase-2, the essential structural features for human cyclooxygenase-2 inhibitors and 3D-Quantitative structure activity relationship (3D-QSAR) model were carried out based on dataset from three confirmatory bioassays using Phase program. Six point pharmacophore (AAHRRR) of COX-2 selective inhibitors was generated from training set of 52 compounds. The 3D-QSAR model was selected as having favourable statistic measures (R2 = 0.93, Q2ext = 0.81) for the training set and test set respectively. This model was developed using the best pharmacophore hypothesis that helped to reveal the essential features responsible for the anti-inflammatory activity. As a result, this pharmacophore hypothesis has aided in the identification of new four natural lead compounds from UNPD database (UNPD100208, UNPD168234, UNPD91145, UNPD57376) that can be used as potential anti-inflammatory agents or as a core structure to develop other more selective molecules. This result was confirmed by molecular docking, which showed that these four natural lead-compounds adopt the same orientation as Rofecoxib in the COX-2 active site. On the other hand, a molecular dynamic simulation (MDS) was applied and repeated on the top ranking complex 5KIR-UNPD100208 and compared with the results of MDS of 5KIR-Rofecoxib. The results from MDS revealed a good stability of the compound UNPD100208 in the active site based on several parameters such as RMSD, RMSF and potential energy, which can nominate it as a natural anti-inflammatory lead-compound candidate.

Cleome arabica leaf extract has anticancer properties in human cancer cells.

CONTEXT: Cleome arabica L. (Capparidaceae) is a desert plant widely distributed in the North part of Africa whose leaves are used in traditional medicine as a sedative for abdominal and rheumatic pains. OBJECTIVES: The anticancer activity of methanol Cleome arabica leaf extracts (CALE) is investigated in different human cancer cell lines. MATERIALS AND METHODS: Five different human cancer cell lines, representative of the most common cancers in Western countries (i.e., breast adenocarcinoma, colon carcinoma, neuroblastoma, hepatoma, cervix carcinoma) were treated with different concentrations of CALE (i.e., 1, 5, 10, 25, 50, 100 and 200 µg/ml). Cell viability and cell cycle were measured by using a hemocytometer chamber and a cytofluorimeter, respectively. Epidermal growth factor (EGF) was used as a positive control. Western blots were performed to evaluate the CALE effects on pathways involved in cell growth regulation and on apoptotic cascade activation. RESULTS AND CONCLUSION: Our results confirm that CALE has a high content of polyphenolic compounds (i.e., 32.21 ± 3.44%), mainly as flavonoids (24.56 ± 4.67%). In all tested cell lines CALE treatment reduces cell number in a dose-dependent manner (ED50 = 175 ± 30 µg/ml). CALE (100 and 200 µg/ml) increases by three-fold the activation of the apoptotic cascade involving caspase-3 activation and the cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Intriguingly, CALE treatment (200 µg/ml) also blocks EGF-induced cell growth by preventing the growth factor-triggered AKT and ERK phosphorylation. As a whole, these data strongly suggest that CALE possesses anticancer effects in all tested cancer cell lines.