Marcella Corda

New halogenated phenylcoumarins as tyrosinase inhibitors

With the aim to find out structural features for the tyrosinase inhibitory activity, in the present communication we report the synthesis and pharmacological evaluation of a new series of phenylcoumarin derivatives with different number of hydroxyl or ether groups and bromo substituent in the scaffold. The synthesized compounds 5-12 were evaluated as mushroom tyrosinase inhibitors showing, two of them, lower IC(50) than the umbelliferone. Compound 12 (IC(50)=215 μM) is the best tyrosinase inhibitor of this series.

Tyrosinase inhibitor activity of coumarin-resveratrol hybrids.

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl)-6,8-dihydroxycoumarin (8) is the most potent compound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

Sexual and seasonal variability of lobster hemocyanin

Abstract 1. 1. Hemocyanin from the mediterranean lobster Palinurus elephas has been shown to change in subunit composition with relation with the sex of the animal and the period of the year. 2. 2. The sexual difference, consisting of the presence of a specific subunit in the hemocyanin from female animals, is not linked to any evident functional property of the pigment. 3. 3. On the contrary, the season dependent variations in the subunit composition, which consist of the appearance of several catodic bands on electropherograms from both male and female animals, produce obvious functional effects; in particular an increase of the cooperativity of oxygen binding has been consistently found during the summer. 4. 4. The concentration of the pigment is also season and sex dependent, being higher in male animals and during the winter. 5. 5. Hemocyanin from a closely related lobster, Palinurus mauritanicus, does not show sexual and seasonal differences in subunit composition. This difference is tentatively attributed to the difference in the habitat of the two species.

PEG-immobilization of cardol and soluble polymer-supported synthesis of some cardol–coumarin derivatives: Preliminary evaluation of their inhibitory activity on mushroom tyrosinase

In this work, the PEG-immobilization and the liquid phase synthesis of some coumarins derived from cardol are presented. Some preliminary results on their tyrosinase inhibitory activity are also included.

Synthesis and biological evaluation of a novel series of bis-salicylaldehydes as mushroom tyrosinase inhibitors.

A series of novel bis-salicylaldehydes were synthesised and evaluated as tyrosinase inhibitors using a tyrosinase-dependent L-DOPA oxidation assay. The bis-salicylaldehydes exhibited greater inhibitory activity than salicylaldehyde. Our data suggests that these novel compounds may serve as a structural template for the design and development of novel tyrosinase inhibitors.

Tyramine oxidation by copper/TPQ amine oxidase and peroxidase from Euphorbia characias latex

Tyramine, an important plant intermediate, was found to be a substrate for two proteins, a copper amine oxidase and a peroxidase from Euphorbia characias latex. The oxidation of tyramine took place by two different mechanisms: oxidative deamination to p-hydroxyphenylacetaldehyde by the amine oxidase and formation of di-tyramine by the peroxidase. The di-tyramine was further oxidized at the two amino groups by the amino oxidase, whereas p-hydroxyphenylacetaldehyde was transformed to di-p-hydroxyphenylacetaldehyde by the peroxidase. Data obtained in this study indicate a new interesting scenario in the metabolism of tyramine.

Flight and heat dissipation in birds a possible molecular mechanism

Birds during normal sustained flight must be able to dissipate more than 8 times as much heat as during rest in order not to be overheated. The experiments reported in this note on the hemoglobin systems from two different birds indicate the existence of a molecular mechanism by which hemoglobin is used simultaneously for oxygen transport and heat dissipation.

Tyrosine-like condensed derivatives as tyrosinase inhibitors

Objectives  We report the pharmacological evaluation of a new series of 3‐aminocoumarins differently substituted with hydroxyl groups, which have been synthesized because they include in their structures the tyrosine fragment (tyrosine‐like compounds), with the aim of discovering structural features necessary for tyrosinase inhibitory activity.

A preliminary study on serum proteomics in fibromyalgia syndrome

Fibromyalgia syndrome (FMS) is a complex illness to diagnose and treat, which presents symptoms that may be part of, or overlap with other diseases or syndromes. The most widely used diagnostic criteria are those of the American College of Rheumatology [1]; no laboratory test has been validated for FMS diagnosis which remains primarily clinically based. Oxidative stress has been proposed as a relevant event in the pathogenesis of FMS with an increase of lipid peroxidation (LPO) [2] and a decrease in vitamin A and E concentrations [3]. Although the etiology of FMS remains unclear, genetic predisposition is likely to be an important factor and transmission is thought to be polygenic [4, 5]. If FMS is a multi-genetic disease then it could be hypothesized that differences exist in the type of proteins or protein expression levels in sera of FMS patients compared with healthy controls. Proteomic analysis is a powerful tool for the global evaluation of protein expression and plays a central role in clinical diagnosis and monitoring. Some studies [6] reported interesting proteomic analysis data with an overexpression of transaldolase and phosphoglicerate mutase I in salivary fluid of FMS patients and focused on the role of oxidative stress in the pathogenesis of the disease. The aim of this preliminary study was to evaluate, using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), changes in protein profiles of FMS patients with respect to control subjects to identify potential serum biomarkers useful for disease diagnosis and management. Sixteen females (52 ± 12 years) affected by FMS and 12 healthy females (48 ± 13 years) were enrolled; all patients fulfilled new ACR diagnostic criteria [1] (Table 1). The presence of a major clinical condition other than fibromyalgia was excluded by physical examination and routine blood and urine screening. No patients suffered of thyroid dysfunction. Psychiatric examination data of patients were reported in a previous study [7]. Study was approved from our Local Ethical Committee and informed consent was obtained from all subjects. Serum protein concentrations were quantified using the PlusOne 2D Quant Kit (GE Healthcare); first dimension isoelectric focusing (IEF) was carried out with 18 cm immobilized pH gradient strips of pH 3–10. The IPG strips were applied onto 10% acrylamide sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) slab gels (25.5 cm × 20.5 cm × 1.0 mm) and overlaid with a solution of 0.5% agarose with a trace of bromophenol blue. Gels were fixed, stained with Coomassie Brilliant Blue G-250 colloidal for 24 h and stored at room temperature. At least three sample replicates were performed. 2D data were processed with Progenesis SameSpots software, which computed multiplication fold, false discovery rate (FDR) q-value, p-values of all spots using one-way ANOVA analysis. A p-value < 0.05 was considered statistically significant; no difference has been found in protein expression according to patient therapy. After normalization, volume calculation and statistical analysis, same data differences were observed between *Corresponding author: Dr. Antonella Fais, Dipartimento di Scienze della Vita e dell’Ambiente, Università di Cagliari, 09042 Monserrato, Cagliari, Italy, Phone: +39 0706754506, Fax: +39 0706754523, E-mail: fais@unica.it Valeria Ruggiero and Enrico Cacace: Dipartimento di Scienze Mediche “Mario Aresu”, Università di Cagliari, Monserrato, Cagliari, Italy Benedetta Era, Marcella Corda and Stefania Utzeri: Dipartimento di Scienze della Vita e dell’Ambiente, Università di Cagliari, Monserrato, Cagliari, Italy Laura Molin: CNR-ISTM, Corso Stati Uniti 4, Padova, Italy

Whale (Balaenoptera physalus) haemoglobin: primary structure, functional characterisation and computer modelling studies

The functional properties of haemoglobin from the Mediterranean whale Balaenoptera physalus have been studied as functions of heterotropic effector concentration and temperature. Particular attention has been given to the effect of carbon dioxide and lactate since the animal is specialised for prolonged dives often in cold water. The molecular basis of the functional behaviour and in particular of the weak interaction with 2,3-diphosphoglycerate is discussed in the light of the primary structure and of computer modelling. On these bases, it is suggested that the A2 (Pro-->Ala) substitution observed in the beta chains of whale haemoglobin may be responsible for the displacement of the A helix known to be a key structural feature in haemoglobins that display an altered interaction with 2,3-diphosphoglycerate as compared with human haemoglobin. The functional and structural results, discussed in the light of a previous study on the haemoglobin from the Arctic whale Balaenoptera acutorostrata, give further insights into the regulatory mechanisms of the interactive effects of temperature, carbon dioxide and lactate.