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A simple approach to aromatization of steroidal quinols and epoxyquinols using a catalytic amount of TMSOTf is reported. Beside acetylation of the angular OH, the acid-catalyzed (TfOH) dienone-phenol rearrangement occurred affording "para" products, or in the case of blocked position 4, the acetoxy group 1,2-migration leads to the formation of "meta" products. Using epoxyquinol derivative as a substrate, the acetoxy group elimination was observed, followed by acid-catalyzed epoxy-ring opening and subsequent double bond migration, giving as a final product Delta(9,11) A-ring aromatized compounds. Synthesis of conduritol-like compounds and structure confirmation by X-ray crystallography of the precursor of steroidal conduritol is also described. In addition, the results of extensive antiproliferative screening against a panel of 60 cancer cell lines are presented. (c) 2005 Elsevier Inc. All rights reserved.

Several cis and trans bis-steroidal 1,2,4,5-tetraoxanes possessing amide terminus were synthesised and evaluated as antimalarials and antiproliferatives. The compounds exhibited submicromolar antimalarial activity against Plasmodium falciparum D6 and W2 strains. The existence of HN-C(O) moiety was found necessary for pronounced antimalarial and antiproliferative activity. In antiproliferative screen, the trans tetraoxane 6 was found to exhibit a pronounced cytotoxicity on 14 cancer cell lines. In addition, tetraoxanes 11 and 12 exhibited significant cytotoxic activity too; microscopic examination of treated HeLa cells showed morphological appearance reminiscent for apoptosis (condensed and/or fragmented nuclei). (C) 2003 Elsevier Science Ltd. All rights reserved.

A lectin from the Adriatic sponge Haliclona cratera was purified by ion-exchange and gel chromatography The molecular mass of the lectin is approximately 29 kDa. Purified lectin is rich in hydrophobic and basic amino acids and has an isoelectric point at pH 8.6. H. cratera lectin is relatively heat- and pH-stable. It agglutinates native and trypsinized, papainized and neuraminidase-treated human A, B, O, AB and sheep erythrocytes, and the hemagglutinating activity is independent of Ca2+, Mn2+ and Mg2+ ions; D-galactose and N-acetyl-D-galactosamine are found to be moderate inhibitors of the activity. H. cratera lectin displays cytotoxic effect on HeLa and FemX cells and weak mitogenic effect on human T-lymphocytes pretreated with phytohemagglutinin (PHA). (C) 2002 Elsevier Science Inc. All rights reserved.

Purpose of this work was to synthesize several cis-/trans- isomer pairs of the platinum(II) complexes, and study the extent and the mode of their antiproliferative activity on HeLa cells. Six platinum(II) isomer pairs have a general formula cis-/trans-[PtA(2) X-2] where A is ligand: ammonia (NH3), pyridine (Py); and X is ligand: chloride ion (Cl-), bromide ion (Br-), iodide ion (I-), thiocyanato, ion (SCN-); four compounds have different structural formulas, and these are cis-/trans-[Pt(NH2OH)(2) (NH3)(2)]Cl-2, and cis-/trans- Pt(Gly)(2), where Gly is bidentate glycinato ligand. Results of the MTT assay, showed that six cis- and one trans-platinum(II) complexes exhibited cytotoxicity (IC50) ranging between 5 and 33 muM. Most of the cis-platinum(II) isomers caused significant alteration of cell cycle phases progression, and induced apoptosis in degree that varied among different compounds, as evaluated using flowcytometry and morphological study. Spectrophotometric analysis (AAS) indicated that there is no correlation between intracellular platinum(II) accumulation and cytotoxicity of tested complexes.

Based on biological properties of epoxyquinols from natural sources, bromo and epoxyquinols derived from estrone were synthesized and screened against Fem-X. HeLa and K-562 cell lines. Evidence was found that the bromine atom and the epoxy moiety significantly increase the antiproliferative activity within the series. (C) 2001 Elsevier Science Ltd. All rights reserved.

Cholic acid-derived 1,2,4,5-tetraoxanes were synthesized in order to explore the influence of steroid carrier on its antimalarial and antiproliferative activity in vitro. Starting with chiral ketones, cis and trans series of diastereomeric tetraoxanes were obtained, and the cis series was found to be similar to 2 times as active as the trans against Plasmodium falciparum DG and W2 clones. The same tendency was observed against human melanoma (Fem-X) and human cervix carcinoma (HeLa) cell lines. The amide C(24) termini, for the first time introduced into the carrier molecule of a tetraoxane pharmacophore, significantly enhanced both antimalarial and antiproliferative activity, as compared to the corresponding methyl esters, with cis-bis(N-propylamide) being most efficient against the chloroquine-susceptible D6 clone (IC50 = 9.29 nM). cis- and trans-bis(N-propylamides) were also screened against PBMC, and PRA-stimulated PBMC, showing a cytotoxicity/antimalarial potency ratio of 1/10 000.

Based on the biological properties of epoxyquinols from natural sources, the title compound was synthesised as a potential antitumor agent. Its molecular structure was partially confirmed by NMR studies. The detailed structure was established by X-ray analysis revealing two symmetry independent molecules in the asymmetric unit each consisting of four fused rings with the C(10) beta-oriented hydroxy group and beta-oriented O atom bridging C(4) and C(5). The conformation of A ring in both conformers A and B is boat (B-3,B-6), while rings B and C are chairs (C-1(4)) and the five-membered D ring is in an envelope (E-2) conformation. The in vitro antitumor activity of title compound and its 17 beta-acetoxy analogue against HeLa and Fem-x cells revealed IC50 values of 5.7 and 7.1 mu M, and 2.25 and 1.58 mu M, respectively. Corresponding quinols were tested on 47 cell lines with 10 beta-hydroxy-17 beta-acetoxyestra-1,4-dien-3-one being most active against leukemia SR cells (GI(50) = 0.17 mu M).