Identification of novel potential cyclooxygenase-2 inhibitors using ligand- and structure-based virtual screening approaches.

Cyclooxygenase 2 (COX-2) is a well-established target for the design of anti-inflammatory intermediates. Celecoxib was selected as a template molecule to perform ligand-based virtual screening, i.e. to search for structures with similarity in shape and electrostatic potential, with a gradual increase in accuracy through the combined fitting of several steps using eight commercial databases. The molecules ZINC408709 and ZINC2090319 reproduced values within the limits established in an initial study of absorption and distribution in the body. No alert was fired for possible toxic groups when these molecules were subjected to toxicity prediction. Molecular docking results with these compounds showed a higher binding affinity in comparison to rofecoxib for the COX-2 target. Additionally, ZINC408709 and ZINC2090319 were predicted to be potentially biologically active. In in silico prediction of endocrine disruption potential, it was established that the molecule ZINC2090319 binds strongly to the target related to cardiovascular risk in a desirable way as a non-steroidal antagonist and ZINC408709 binds strongly to the target that is associated with the treatment of inflammatory pathologies and similar to celecoxib. Metabolites generated from these compounds are less likely to have side effects. Simulations were used to evaluate the interaction of compounds with COX-1 and COX-2 during 200 ns. Despite the differences, ZINC408709 molecule showed better stability for COX-2 during molecular dynamics simulation. In the calculations of free energy MM/PBSA, the molecule ZINC408709 ΔGbind value has a higher affinity to celecoxib and rofecoxib COX-2. This demonstrates that the selected substances can be considered as promising COX-2 inhibitors. Communicated by Ramaswamy H. Sarma.

Does total tannin content explain the use value of spontaneous medicinal plants from the Brazilian semi-arid region?

Due to the current predatory exploitation and consequent extinction of native medicinal plants around the world, strategies have been proposed aiming at the sustainable use of these resources. Accordingly, this study aims at verifying the differences in tannin compounds content in the bark of eleven species with high use value (UV) and also relating the amounts of tannins with their therapeutic indications. To quantify the total phenolic content in the samples the Folin-Ciocalteu reagent was used, and for total tannins chemical casein precipitation was applied. The amount of tannins ranged intra-specifically and the greater variation was found for Anadenanthera colubrina (angico) that displayed between 157.57 and 107.39 mg/g. The lowest variation occurred in Lafoensia replicata (mangabeira) with values ranging between 76.55 and 68.96 mg/g. There were significant differences between several of the eleven species and according to the simple regression analysis, the quantities of tannins found failed to justify their UV. Thus, it was not possible to establish whether the amount of total tannins influenced to a greater or lesser degree in the accumulation of knowledge. Moreover, this is the first study to investigate the relationship between the amount of total tannins and local botanical knowledge expressed by the UV.