Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.

The effect of low doses of echinochrome A (EchA), a natural polyhydroxy-1,4-naphthoquinone pigment from the sea urchin Scaphechinus mirabilis, has been studied in clinical trials, when it was used as an active substance of the drug Histochrome® and biologically active supplement Thymarin. Several parameters of lipid metabolism, antioxidant status, and the state of the immune system were analyzed in patients with cardiovascular diseases (CVD), including contaminating atherosclerosis. It has been shown that EchA effectively normalizes lipid metabolism, recovers antioxidant status and reduces atherosclerotic inflammation, regardless of the method of these preparations' administrations. Treatment of EchA has led to the stabilization of patients, improved function of the intracellular matrix and decreased epithelial dysfunction. The increased expression of surface human leukocyte antigen DR isotype (HLA-DR) receptors reflects the intensification of intercellular cooperation of immune cells, as well as an increase in the efficiency of processing and presentation of antigens, while the regulation of CD95 + expression levels suggests the stimulation of cell renewal processes. The immune system goes to a different level of functioning. Computer simulations suggest that EchA, with its aromatic structure of the naphthoquinone nucleus, may be a suitable ligand of the cytosolic aryl cell receptor, which affects the response of the immune system and causes the rapid expression of detoxification enzymes such as CYP and DT diaphorase, which play a protective role with CVD. Therefore, EchA possesses not only an antiradical effect and antioxidant activity, but is also a SOD3 mimetic, producing hydrogen peroxide and controlling the expression of cell enzymes through hypoxia-inducible factors (HIF), peroxisome proliferator-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR).

Preparative Synthesis of Spinochrome D, a Pigment of Different Sea Urchin Species.

A simple and effective synthesis of spinochrome D (1) (2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), a pigment of different sea urchin species, has been developed starting from 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (13), easily available by cycloacylation of 1,4-dimethoxybenzene (11) with dichloromaleic anhydride (12). Bromination of 13 with either bromine or dioxane dibromide to 6-bromo-2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (21), followed by nucleophilic substitution of the halogen atoms by methoxy groups in 21 and hydrolysis of trimethyl ether 10 produce the target compound in overall yield from 62 to 65%.

Preparative production of spinochrome E, a pigment of different sea urchin species.

A concise route to spinochrome E (1) (2,3,5,6,7,8-hexahydroxy-1,4-naphthoquinone), a pigment isolated from sea urchins of different species, has been developed starting from either commercially available 5,8-dihydroxy-1,4-naphthoquinone (11) or 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (12). The protocol involves 3 steps, the chlorination of either 11 or 12 to tetrachloronaphthazarin (13), the total nucleophilic substitution of the chlorine atoms in 13 by methoxy groups, and hydrolysis of tetramethyl ether14; this makes possible the preparation of the target compound in overall yields from 41 to 46%.

Magnetic resonance imaging of mouse Ehrlich carcinoma growth inhibition by thiacarpine, an analogue of cytotoxic marine alkaloid polycarpine.

The anticancer effect of thiacarpine, a synthetic analogue of the known cytotoxic alkaloid polycarpine isolated from the Pacific ascidian Polycarpa aurata, was investigated in vivo in experiments using mouse solid Ehrlich carcinoma tumor as the target. A high-resolution magnetic resonance imaging (MRI) technique using a MR tomograph "PharmaScan" US70/16 (Bruker, Ettlingen, Germany) was used for visualization and quantification of tumor size. Fluorescence microscopy and image analysis were applied to determine Ehrlich carcinoma cell chromatin condensing (apoptosis) and necrosis in Ehrlich carcinoma cells at the action of thiacarpine in in vitro experiments. The scan and size calculations of the tumor and some mouse organs were carried out during the experiments. Thiacarpine in a total dose of 100 mg/kg was found to exhibit the delay in growth of the mouse tumor. The antineoplastic effect of this compound was accompanied by an increase in the lifetime of experimental mice in comparison with the control group of animals. Our data show that the ability of thiacarpine to induce apoptosis in carcinoma cells may contribute to thiacarpine anticancer effects against mice solid Ehrlich carcinoma in vivo detected by MRI.