Drug Repurposing on G Protein-Coupled Receptors Using a Computational Profiling Approach.

G protein-coupled receptors (GPCRs) are the largest human membrane receptor family regulating a wide range of cell signaling. For this reason, GPCRs are highly desirable drug targets, with approximately 40% of prescribed medicines targeting a member of this receptor family. The structural homology of GPCRs and the broad spectrum of applications of GPCR-acting drugs suggest an investigation of the cross-activity of a drug toward different GPCR receptors with the aim of rationalizing drug side effects, designing more selective and less toxic compounds, and possibly proposing off-label therapeutic applications. Herein, we present an original in silico approach named "Computational Profiling for GPCRs" (CPG), which is able to represent, in a one-dimensional (1D) string, the physico-chemical properties of a ligand-GPCR binding interaction and, through a tailored alignment algorithm, repurpose the ligand for a different GPCR. We show three case studies where docking calculations and pharmacological data confirm the drug repurposing findings obtained through CPG on 5-hydroxytryptamine receptor 2B, beta-2 adrenergic receptor, and M2 muscarinic acetylcholine receptor. The CPG code is released as a user-friendly graphical user interface with numerous options that make CPG a powerful tool to assist the drug design of GPCR ligands.

Comparative study on the occurrence of polycyclic aromatic hydrocarbons in breast milk and infant formula and risk assessment.

The study compared the polycyclic aromatic hydrocarbons (PAH) profile of human milk collected from Italian mothers and different brands of infant formula available on Italian market. Levels of 14 PAHs most frequently occurred in food, PAH markers listed by Commission Regulation (EC) No. 1881/2006, and carcinogenic PAHs classified by the International Agency for Research on Cancer, were determined by high-pressure liquid chromatography with fluorescence detector. The average concentrations of total PAHs were 114.93 in breast milk and 53.68 µg kg-1 in infant formula. Furthermore, Benzo(a)pyrene (BaP) and the sum of ∑PAH4 markers (BaP, Chrysene, Benzo(a,h)anthracene and Benzo(b)fluoranthene) were higher than the permissible limit of 1 µg kg-1 in 43% and 86% for breast milk and in 10% and 76% for infant formula samples, respectively. Breast milk showed higher levels (P < 0.05) of carcinogenic, and possible carcinogenic hydrocarbons than infant formula samples. Both in human and commercial milk, data showed the occurrence of low and high molecular weight PAHs, respectively from petrogenic and pyrolytic environmental sources, characterizing the infant and mother exposure. Particularly, waste incineration could have represented an important exposure source for infants during breastfeeding, through exposition of mothers resident in some areas of Southern Italy. High PAH levels detected in infant formula enriched with LC-PUFA might be related to the contamination of the vegetable oils added as ingredients. Results showed a high percentage of samples of both breast milk and infant formulas with margin of exposure (MOE) value indicating a potential concern for consumer health.

Occurrence and distribution of polycyclic aromatic hydrocarbons in mussels from the gulf of Naples, Tyrrhenian Sea, Italy.

To assess the potential impact of the industrial activity on food safety and risk for consumers, the aim of the study was to evaluate the levels of 14 polycyclic aromatic hydrocarbons (PAH) in 69 samples of wild and farm Mytilus galloprovincialis, collected in sites of coast of Gulf of Naples, Tyrrhenian Sea. All hydrocarbons were found in samples. Higher levels of pyrolytic PAHs were in wild than in farm mussels. Benzo(a)pyrene exceeded the Regulation (EC) n.835/11 levels of 1 µg/kg in 15 samples (71.42%) of wild and 25 samples (65.79%) of farm mussels. System of sum of 4 hydrocarbons exceeded the law level in 15 samples (71.42%) of wild and 21 samples (55.26%) of farm mussels. Wild mussel levels showed a potential impact of pyrolytic sources of PAH on food safety. Occurrence of carcinogenic PAHs should be a cause for concern, in areas where the mussels are being farmed for human consumption.