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Objective: Parkinson's disease (PD) is often characterized by altered emotional processing, such as depression and alexithymia. Alexithymic and depressive symptoms may be partially overlapping and the relative independence of these two disorders is strongly debated. Reduced echogenicity of midbrain raphe, evaluated with transcranial sonography (TCS), is a characteristic finding in depression associated with PD. No data are available on brainstem's echogenicity in alexithymic PD patients. We assessed, by means of transcranial sonography, possible differences between PD patient with or without alexithymia and/or depression. Methods: We recruited 22 PD patients among our local cohort of 200 patients referred to our Movement Disorder Center during 2014. All patients were treated with optimal dose of dopaminomimetic (L-DOPA EQ mg 499.7 ± 256.3) and underwent neuropsychological tests including Beck Depression Inventory (BDI) and Toronto Alexithymia Scale-20 (TAS-20). Motor symptoms were assessed with Unified Parkinson's Disease Rating Scale (UPDRS III) and modified Hoehn and Yahr scale (H&Y). TCS was performed, through temporal window, using a color-coded phasedarray ultrasound system (SONOS 7500), to evaluate midbrain raphe (0=absent, 1=discontinuous, 2=continuous). Results: TAS-20 and BDI identified 4 patients with depression without alexithymic symptoms (18.18%), 7 alexithymic patients without depression (31.82%), 5 PD patients with depression and alexithymia (22.73%) and 6 PD patients without any of the two disorders (27.27%). At statistical analysis hypoechogenicity correlated with BDI score and the presence of alexithymia was not significantly correlated with absent or discontinuous raphe. Conclusion: The study evidenced the presence of hypoechogenicity in the midbrain raphe in PD patient with depression. No alteration of midbrain raphe was found in PD patients with alexithymia. These findings suggest that while depression in PD may involve central component of brainstem midline, constituting the basal limbic system, called mesocorticolimbic pathway, alteration in alexithymia does not affect the midbrain. This study provides further evidence that depression and alexithymia are independent affective disorder.

There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. A number of quinones have been shown to be effective antimalarials; the observed effects are most likely related to the most prominent chemical feature of these kind of molecules, that is their ability to undergo redox cycling. Antiplasmodial activity of quinone structures of marine origin has been reported. Examples are xestoquinone and halenaquinone (Laurent et al., 2006, Bioorg. Med. Chem., 14:4477-82), their derivative orlaquinone (Longeon et al., 2010, Bioorg. Med. Chem., 18:6006-11), and ketoadociaquinones (Shmitz et al., 1988, J. Org. Chem., 53:3922-25; Cao et al., 2005, Bioorg. Med. Chem., 13:999-1003), isolated from Xestospongia sponges, and thiaplakortones (Davis et al., 2013, J. Org. Chem., 78: 9608-13), isolated from Plakortis lita. It has been also evidenced that the presence of a dioxothiazine moiety enhances the antiplasmodial activity (Figure 1). Within our search for bioactive compounds from Mediterranean ascidians, we have previously isolated a large group of thiazinoquinones (Menna et al., 2013, Eur. J. Org. Chem,, 16:3241-46; Aiello et al., 2005, Eur. J. Org. Chem., 23:5024-30; Aiello et al., 2005, J. Med. Chem., 48:3410-16; Aiello et al., 2003, Eur. J. Org. Chem., 5: 98-900). Some of these compounds have been used as lead structures for the synthesis of simplified analogues for pharmacological screening (Aiello et al., 2010, Bioorg. Med. Chem., 18: 719-27). Based on the structural analogy with the reported antimalarial quinone structures, the synthetic derivatives prepared using the natural thiazinoquinones aplidinones A and B as model structures (1-12, Figure 2) have been tested in vitro against D10 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains of P. falciparum. The synthetic derivatives have shown a significant antiplasmodial activity and many structural requirements, critical for their activity, have been evidenced. Conformational (MD and MM) and electronic (tautomeric form, pka values, percentage of neutral/ionized forms at different pH values) analysis have been performed by computational means. The propensity for electron acceptance of the active compounds has been explored by LUMO orbital and anionic radical analysis. A correlation between electrochemistry (???direct??? and in the presence of Fe(III)-Heme) of the studied compounds and their antiplasmodial effects has been evidenced by using solid-state electrochemical assays (Dome??nech-Carbo?? et al., 2013, Anal. Chem., 85: 4014-21).

Chemical investigation of the Mediterranean ascidian A.conicum resulted in the isolation of two new meroterpenes, the conithiaquinones A (1) and B (2), in addition to two previously reported chromenols (3 and 4) and conicaquinones (5 and 6). The structures of conithiaquinones A and B were determined by interpretation of spectroscopic data, and regiochemical and stereochemical assignments were achieved with the aid of computational methods, including the recently developed DP4 NMR spectral prediction method. Both conithiaquinones A and B showed significant effects on the growth and viability of cells, with 1 showing interesting cytotoxicity against human breast cancer cells.

Complex polysubstituted alkyl sulfates have been isolated from ascidians; a remarkable example is turbinamide, a bioactive metabolite isolated in our laboratory from Sidnyum turbinatum. This molecule demonstrated a strong and selective cytotoxic effect against neuronal rather than immune system cells. We have indeed isolated two new sulphated compounds (1 and 2) from another collection of S. turbinatum; as well as two new molecules (3 and 4) from two different Mediterranean ascidians (Sidnyum elegans and Ciona edwardsii). Their structural analogy with turbinamide allowed evaluating the influence of slight structural modifications on the activity.

Betaines and similar zwitterionic compounds are widely distributed in terrestrial plants and algae, as well as in marine invertebrates. In biological systems, these highly soluble dipolar molecules serve as organic osmolytes (osmoprotectants), namely substances synthesized or taken up from the environment by cells for protection against osmotic stress. Osmoprotectants can stabilize proteins and membranes when salt levels or temperatures are unfavourable; therefore, they could play important roles in the adaption of cells of marine invertebrates to various adverse environmental conditions. Examples of betaines isolated from marine invertebrates are homarine,1 trigonelline,2 taurines, baikiain betaine,3 β-stachydrine, 4 nor- and aminozooanemonin, 5 pyridinebetaines A and B.5 Most of these compounds are amphoteric low-molecular weight quaternary ammonium compounds deriving from proteinogenic or non- proteinogenic amino acids in which the nitrogen atom if fully methylated. Within a recent investigation of alkaloids from Axinella sponges, we have examined specimens of Axinella polypoides collected along Sardinian coasts and we have isolated three novel unique compounds, polyaxibetaines A-C (1-3), whose structure elucidations are the subject of this paper.Polyaxibetaines A-C extend the structural variety of the so far known betaines; in compounds 1 and 2, indeed, the nitrogen atom of the -amino group of phenylalanine and tyrosine, respectively, is comprised in a piperidine ring and further methylated, while compound 3 is a pyridine derivative sharing the nitrogen atom with the alfa-amino group of a tyrosine residue.

Ascidians belonging to the Aplidium genus are characterized by a great chemiodiversity that includes nitrogenous and non-nitrogenous metabolites, this latter group being dominated by prenyl quinones/hydroquinones, linear or cyclic derivatives1. These compounds are generally known as meroterpenes. Recently, we analyzed a sample of Aplidium conicum collected in the Bay of Naples and, surprisingly, the pattern of its secondary metabolites resulted very different from that of other samples of A. conicum previously investigated. In fact, the ascidian is completely lacking in meroterpenoids, whilst the main components of its methanolic extract are a new class of molecules, unsaturated linear alkylsulfoxides, whose major constituents are Conisulfamines A, B, and C. The structures of the new compounds have been elucidated through an extensive application of MS, 1H, 13C and 2D homo-and heteronuclear-NMR techniques. The stereochemical analysis of Conisulfamine A has been carried out in a three stages–approach, relying on the combination of NMR spectroscopy and computational methods.