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An ever-increasing incidence of skin neoplastic diseases is registered. Therefore, it is important to protect the skin from the UV radiation that reaches the epidermis and dermis but also to block ROS generated by them. Our attention was attracted in developing new compounds provided with both UV filtering and antioxidant capacities. To this end, 2-phenyl-1H-benzimidazole-5-sulfonic acid (PBSA), a known UV filter, was selected as lead compound for its lack of antioxidant activity, high water solubility and good safety profile. PBSA was sequentially modified introducing hydroxyls on the phenyl ring and also substituting the functional group in position 5 of the benzimidazole ring. At the end of the synthetic study, a new, very potent class of antioxidants has been obtained. Surprisingly some of the developed molecules, while devoid of significant UV-filtering activity was endowed with potent UV-filtering booster capability if associated with known commercial UVB and UVA filters.

Zinc proteinases have been recognized as a distinct class of proteolytic enzymes in which at least one ion of zinc is involved directly in catalysis. This family includes a growing number of biologically important enzymes which are attractive targets for rational drug design. In this paper we examine the special features of the zinc binding environment of these enzymes in order to gain information which could be useful in the preparation of 'zinc-directed' selective inhibitors. Carboxypeptidase A (CPA) is presented as a model for one class of zinc proteinases, and the active-site zinc and its interactions are examined with the primary focus on geometrical considerations. The three-dimensional structure of the native and apoenzyme are discussed, together with the high-resolution structure of several enzyme-inhibitor complexes. This paper will first present a structural analysis of CPA derivatives and then discuss a series of zinc model compounds which have been prepared and characterized in order to examine the ligand and geometrical preferences of the zinc in an unstrained system. X-ray crystallography (macromolecular and small molecule) is the main experimental method used for the structural analyses, while complementary computational methods have been used for the examination of electrostatic potentials. The results from the various experimental efforts are assembled in order to draw general conclusions on the potential use of the zinc ion as the primary target for inhibitor binding. The results of these studies suggest that the zinc ion is important for both the binding and the catalytic activation of the substrate as well as for stabilization of the tetrahedral reaction intermediate.

Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin-Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets.KEY WORDS: DPPH and FRAP tests Folin-Ciocalteu test lipids milk phenolic content proteins soy whey

Hesperidin is one of the most important natural flavonoids, known for its antioxidant, anti-inflammatory, anti-mutagenic, and anti-hypertensive properties. Despite its various biological activities, hesperidin is rarely used in the dermo-cosmetic field because of its poor solubility in both water and oil phases that makes difficult formulation, distribution and bioavailability through the skin layers. Moreover, hesperidin is still underestimated in skin care products, and literature data on its stability into a topical formulation are not yet available. In this paper we report the synthesis of five different derivatives of hesperidin and their evaluation in terms of antioxidant, antifungal, antiproliferative, and apoptotic effects on human leukemic K562 cells. Preliminary antiproliferative effects were considered since hyper-proliferation is involved in several cutaneous problems particularly in the case of photo-exposition and environmental pollution. Esp4 and Esp5 were found to be more active in inhibiting K562 cell growth than parent hesperidin. Esp3 exhibited different biological properties, i.e., antioxidant activity in the absence of antiproliferative effects.

Ultraviolet (UV) light is the most abundant and significant modifiable risk factor for skin cancer and many other skin diseases such as early photo-aging. Across the solar radiation spectrum, UV light is the main cause behind skin problems. In the search for novel photoprotective compounds, a new series of 8-substituted purines were synthesized from commercially available 6-hydroxy-4,5-diaminopyrimidine hemisulfate or 4,5-diaminopyrimidine. All title compounds were investigated for their UV filtering, antioxidant, antifungal, and antiproliferative activities. For the photoprotection assays we used a diffuse transmittance technique to determine the sun protection factor (SPF) in vitro, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) tests for evaluating the antioxidant activity of the more potent compounds. Among them, 8-(2,5-dihydroxyphenyl)-7H-purin-6-ol (compound 26) proved to be a good radical scavenger and is also endowed with broad-spectrum UVA filtering capabilities, suitable for further development as a protective molecule.

Trans -resveratrol (RES) and N-acetylcysteine (NAC) have protective effects on biological processes; therefore, they are frequently included in food supplements. Their possible applications for the prevention of free radical-induced damage to the skin are of particular physiological relevance; however, their usefulness is limited by their metabolic fate and the unpredictability of their delivery to the skin following oral administration. In this work, we evaluated the concomitant and direct application of RES and NAC on the skin using a self-nanoemulsifying system we previously developed for the oral delivery of poorly absorbed food supplements. We evaluated the capability of this system to increase RES and NAC accumulation in porcine skin using permeation studies in Franz diffusion cells. The ascorbyl palmitate (ASP) self-nanoemulsifying system considerably increased RES and NAC accumulation in the epidermis and dermis, which peaked 6 h after application. This study reveals a new formulation strategy to improve the bioavailability of ingredients, which was previously used in the health supplements field, but has rarely been employed in dermatology because of its poor distribution in the skin.