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.

Pharmacophore and QSAR modeling of endothelial nitric oxide synthase inhibitors and subsequent validation and in silico search for new hits

Endothelial Nitric Oxide synthase [eNOS] has an emerging role in chronic inflammation and cancer thus prompting continuous attempts to discover new inhibitors of this enzyme. Towards this end, efforts to discover and optimize new eNOS inhibitors are essential. Therefore, we explored the pharmacophoric space of 151 eNOS inhibitors using ten diverse sets of inhibitors to identify high quality pharmacophores. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing a self-consistent quantitative structure-activity relationship [QSAR] of optimal predictive potential [r[2] [121] = 0.77, F = 63.5, r[2][LOO] = 0.62, and r[2] [PRESS] against 30 external test inhibitors = 0.63]. Interestingly, only one pharmacophore emerged in the optimal QSAR equation. Comparisons with the binding site of eNOS and receiver-operating characteristic [ROC] curves analysis established the validity of this QSAR-selected pharmacophore model. We employed the pharmacophoric model and associated QSAR equation to screen the national cancer institute list of compounds [NCI]

Investigation of the active constituents of portulaca oleraceae L. [portulacaceae] growing in Jordan

The phytochemical analysis of the fresh aerial parts of Portulaca oleracea [Portulacaceae], growing in Jordan, using conventional chromatographic procedures resulted in the isolation of beta-sitosterol, beta-sitosterol-glucoside, N,N'- dicyclohexylurea, and allantoin. The last three compounds were isolated for the first time from this plant. The structure elucidation of these compounds was attained by the use of spectral data [UV, IR, MS, 1H-, 13C- and 2D-NMR], X-ray crystallography and by comparison with authentic samples