Effect of propylene glycol on the skin penetration of drugs.

Propylene glycol (PG) has been used in formulations as a co-solvent and/or to enhance drug permeation through the skin from topical preparations. Two skin in vitro permeation approaches are used to determine the effect of PG on drug penetration. The in vitro Skin-PAMPA was performed using 24 actives applied in aqueous buffer or PG.

Prediction of the skin permeability of topical drugs using in silico and in vitro models.

The main challenge of topically applied drugs is to overcome the skin barrier to reach the site of action at the concentration needed for efficacy. In the research of new topical drugs, design of molecules with optimized properties for skin penetration is a key factor and assays for its characterization are needed. A group of 20 representative topical molecules of clinical use were studied in two in silico models (Potts & Guy and Barratt), and an in vitro assay with artificial membrane (Skin-PAMPA).

Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition.

Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors.

Optimization of xanthatin extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties.

The aqueous extraction of the sesquiterpene lactone xanthatin from Xanthium spinosum L. favours the conversion of xanthinin (1) to xanthatin (2) via the loss of acetic acid. The cytotoxic (Hep-G2 and L1210 human cell lines) and antiviral activities of isolated xanthatin are established.

Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: lead optimization.

Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles.