Annika Lopp

New antiproliferative 9,11-secosterol from soft coral gersemia fruticosa

A new highly antiproliferative 9,11-secosterol 1 was isolated from the White Sea soft coral Gersemia fruticosta. The structure was established

New cytotoxic sterols from the soft coral Gersemia fruticosa

Abstract Six new polyoxygenated sterols 1–6 were isolated from the soft coral Gersemia fruticosa. The structures of these compounds were determined by MS. 1H- and 13C- 1D and 2D FT NMR spectroscopy. Compounds 1–6 showed a moderate cytotoxic activity against human erythroleukemia K-562 cells and other leukemia cell lines.

The effect of 9,11-secosterol, a newly discovered compound from the soft coral Gersemia fruticosa, on the growth and cell cycle progression of various tumor cells in culture

A new 9,11-secosterol, 24-nor-9,11-seco-11-acetoxy-3 beta,6 alpha-dihydroxycholest-7,22(E)-dien-9-one, was found to exhibit growth inhibitory (IC50 below 10 microM) and cytotoxic activities against human leukemia K562, human cervical cancer HeLa, and Ehrlich ascites tumor cells in vitro. The cytostatic concentrations of the compound generally caused the G2/M block in the cell cycle progression, but differences between the three tumor cell lines in the events leading to cell death were remarkable. While inhibiting cell proliferation, 9,11-secosterol caused accumulation of HeLa and K562 cells in the metaphase of mitosis. So, abnormal mitosis can play an important role in the cytotoxicity of 9,11-secosterol in these cell lines. In the Ehrlich ascites tumor cell line the increasing concentrations of the drug (up to 40 microM) did not cause an immediate cell killing. Instead, due to continued DNA synthesis without entry into mitosis, cells with high DNA ploidy were produced. It was shown that the cytoskeletal systems such as microtubules and microfilaments were not damaged by the action of 9,11-secosterol. Further studies are necessary to elucidate the mechanism of the cytotoxic effect of 9,11-secosterol.

Natural occurrence of 2',5'-linked heteronucleotides in marine sponges.

2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′ p5′U, A2′p5′C, G2′p5′A and G2′ p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.

Molecular identification, characterization and distribution of freshwater sponges (Porifera: Spongillidae) in Estonia

This study is the first comprehensive survey of the distribution of freshwater sponges in the rivers of Estonia. The classical morphological method for the identification of freshwater sponges was complemented by a molecular approach, based on sequencing of a DNA region containing a variable D3 domain of the 28S rDNA. This particular segment of 28S RNA proved to be suitable for the discrimination between freshwater sponges at the species level. We showed that Ephydatia fluviatilis was the most widely distributed species followed by Spongilla lacustris and Ephydatia muelleri. Eunapius fragilis was found in a small number of localities and has been described for the first time in Estonia.

Synthesis and antiproliferative activity of 15-oxoprostaglandins: Contribution of the ω-chain enone group to cytotoxicity

Abstract 15-Oxo metabolites of prostaglandins E2, F2α and new 15-oxo prostaglandin analogues 5 and 7 were found to reveal higher antiproliferative activity than the corresponding 15-hydroxy derivatives on human leukemia K562 cells in vitro. The responsibility of the enone group in the ω-chain of a prostanoid molecule for this activity is suggested.