Inhibition of dipeptidyl peptidase IV by fexofenadine: Virtual screening study

Dipeptidyl peptidase IV (DPP IV) is relatively new anti-diabetic target. DPP IV inhibitors lower fasting andpostprandial glucose concentrations by preventing the degradation of the natural hypoglycemic incretin hormones:glucose-dependent insulinotropic peptide and glucagon-like peptide-1. In this work, the high throughput dockingsoftware FRED was used as a virtual screening tool against in house built drug database to discover new DPP IVinhibitors. One of the highest ranking hits, the antihistamine drug fexofenadine, was found to inhibit recombinanthuman DPP IV in vitro with IC50 = 4.6 (±1.0) µM. The anti-diabetic effect of fexofenadine was validated in vivo byoral glucose tolerance test. These results could be helpful in the development of novel DPP IV inhibitors based onfexofenadine scaffold for the treatment of type 2 diabetes.

Evaluation of a binary carrier system for the dissolution enhancement of a high dose poorly soluble drug

The role of two surface active carriers, Gelucire[registered] 44/14 and Lutrol[registered] F127, for improvement of solubility and dissolution of the high-dose, poorly water-soluble drug, albendazole, using solid dispersion approach was evaluated. The solubility of albendazole in solutions of the studied carriers and binary mixtures showed improvement, with solutions containing higher percentages of Lutrol[registered] F127 as best solvents. Albendazole was then incorporated in matrices made of either carrier alone or mixtures of the two carriers at different ratios using a melting procedure. The resulting particles were compressed into tablets. In vitro dissolution of particles and tablets showed fast dissolution. Increased wettability of albendazole by the carriers and formation of partial solid solutions of it in the carrier system were shown to be the mechanisms of the improvement in its dissolution

In vitro xanthine oxidase inhibition by selected Jordanian medicinal plants

In the present study, 18 Jordanian medicinal plants were evaluated for their Xanthine Oxidase [XO] inhibitory potential. Their aqueous extracts, prepared from used parts, were tested in vitro, at 200 micro g/mL concentration, for their inhibition potencies expressed as% inhibition of XO activity. Five of the tested plants were found most active [% inhibition more than 35%] and their inhibition profiles [dose-dependent] were further evaluated by estimating the IC[50] values of their corresponding extracts. These plants were Hyoscyamus reticulates L. [IC[50] = 12.8 micro g/mL], Achillea fragrantissima [Forssk.] Sch. Bip. [197.6 micro g/mL], Pimpinella anism L., [300.4 micro g/mL]. Origanum syriacum L. [317.0 micro g/mL], and Origanum vulgare L. [403.9 micro g/mL]. Moreover, five more plants showed XO inhibitory activity in the range of 14-30%. Namely: Daphne linearifolia L. [29.5% inhibition], Hibiscus sabdoriffa L. [19.44], Aristolochia maurorum L. [15.6%], Citrullus colocynthis [L.] Schr. [14.4%], and Laurus nobilis L. [13.97%]. Considering the results of the present screening study, many of the investigated plants species can be used as potential sources of natural XO inhibitors that can be elaborated as successful herbal remedies for gout, arthritis and other XO-related disorders