The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants and diffusible radical species. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and the initiation and propagation of acute and chronic inflammatory diseases. Because of the deleterious effects of circulating MPO released from phagocytosing neutrophils, there is a great interest in the development of new efficient and specific inhibitors. It has been demonstrated that the interaction between the inhibitor and the active site is not the only key factor playing a role in the inhibition. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening combined to drug-likeness filters. Starting from a set of 727,842 compounds, 30 molecules were selected by this virtual method and tested for inhibition of the chlorination activity of MPO. Twelve out of 30 compounds were found to have an IC50 less than 5 µM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (Zinc1) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (Zinc3) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that Zinc1 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration. Pharmacomodulation has been performed to optimize the activity of Zinc1.

Propolis is a resinous mixture which honey bees collect from buds and bark of some trees. It contains several antioxidant compounds such as polyphenols and flavonoids. This paper describes the antioxidant capacity of propolis extracts and pure polyphenols in vivo. Several biological parameters were measured after promoting oxidative stress. All the homeostasis changes and liver, kidney, and lung damage were restored by propolis extract. Propolis extracts directly modulated lipid peroxidation where LDL level decreased from 1.3 to 0.8 g/L after giving propolis, illustrating the antioxidant contribution of propolis. Finally, orally administered pure antioxidant compounds such as caffeic acid, quercetin, and kaempferol at the doses corresponding to in vitro antioxidant capacity of the propolis extract did not restore the physiological parameters. Bioavailability study demonstrated that the isolated polyphenols have lower absorption (plasma C max of polyphenols 5 15-20 mg/mL) than the complex extract of propolis (plasma C max of polyphenols 5 40-50 mg/mL). Practical applicationsExtracts of propolis showed significant reduction of oxidative damages from oxidative stress. The complexity of propolis has an antioxidant capacity more than its isolated polyphenols. Monitoring the concentrations of the compounds in serum after orally administering of propolis and isolated polyphenols demonstrated that these antioxidant compounds have higher bioavailability when applied as crude extracts. These results make the propolis extracts a promising antioxidant which could be used as a food supplement.

The formation of multi-stimuli responsive polymers exhibiting magnetic, pH and light sensitivity is reported.

Low estradiol level in postmenopausal women is implicated in osteoporosis, which occurs because of the high bone resorption rate. Estrogen formation is controlled by 17-β hydroxysteroid dehydrogenase 17-β HSD enzymes, where 17-β HSD type 1 contributes in the formation of estradiol, while type 2 catalyzes its catabolism. Inhibiting 17-β HSD2 can help in increasing estradiol concentration. Several promising 17-β HSD2 inhibitors that can act at low nanomolar range have been identified. However, there are some specific challenges associated with the application of these compounds. Our review provides an up-to-date summary of the current status and recent progress in the production of 17-β HSD2 inhibitors as well as the future challenges in their clinical application.