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Antiproliferative and antibacterial activities of nine glutarimide derivatives (1–9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6–8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10−3 mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

Partially purified polysaccharides (FP) and hot alkali extract (FNa) obtained from fruiting bodies of the wild basidiomycete Grifola frondosa were examined for their antimicrobial, antioxidant and cytotoxic activity. The structural properties of FP and FNa samples were investigated by FT-IR and high resolution 1H- and 13C-NMR spectroscopy. From a group of various G- and G+ bacteria the antibacterial effects were highest against the G + B. cereus. FNa was the better antioxidant shown by the lower EC50 values of DPPH scavenging ability, ferric-reducing antioxidant power and ferrous ion-chelating ability. Ferric-reducing antioxidant power and ferrous ion-chelating ability were mostly linked to total polysaccharides, total- and beta-glucan content, as well as total protein content. Both extracts displayed a moderate dose dependent antiproliferative action towards malignant human breast cancer MDA-MB-453, cervical adenocarcinoma HeLa and myelogenous leukemia K562 cells not observed in the non cancer derived MRC-5 fibroblasts. The highest effect was found in HeLa cells for FP extract. The mean diameter of Ca-alginate bead loading FP was 960.7 mu m while the mean diameter of beads encapsulating FNa extract was 1051.7 mu m.

The methanolic extract of the wild edible mushroom Cantharellus cibarius Fr. (chanterelle) was analyzed for in vitro antioxidative, cytotoxic, antihypertensive and antibacterial activities. Various primary and secondary metabolites were found. Phenols were the major antioxidant components found in the extract (49.8 mg g(-1)), followed by flavonoids, whose content was approximately 86% of the total phenol content. Antioxidant activity, measured by four different methods, was high for inhibition of lipid peroxidation (EC50 = 1.21 mg mL(-1)) and chelating ability (EC50 = 0.64 mg mL(-1)). The antioxidant activity of the C. cibarius methanol extract was achieved through chelating iron compared to hydrogen atom and/or electron transfer. The extract showed good selectivity in cytotoxicity on human cervix adenocarcinoma HeLa, breast carcinoma MDA-MB-453 and human myelogenous leukemia K562, compared to normal control human fetal lung fibroblasts MRC-5 and human lung bronchial epithelial cells BEAS-2B. The extract had inhibitory activity against angiotensin converting I enzyme (ACE) (IC50 = 0.063 mg mL(-1)). The extract revealed selective antimicrobial activity against Gram-positive bacteria with the highest potential against E. faecalis. The medicinal and health benefits, observed in wild C. cibarius mushroom, seem an additional reason for its traditional use as a popular delicacy food.

The birch polypore Piptoporus betulinus was among two mushrooms that were found in the Iceman's bag. Recent studies indicated that P. betulinus was probably used as a religious and medicinal item. In order to examine the medicinal potential of P. betulinus, hot water (HW), partially purified (PP), and alkali extract (HA) were prepared and tested for antioxidant, antimicrobial, cytotoxic, and angiotensin I-converting enzyme (ACE) inhibitory activity. All tested samples exhibited moderate cytotoxic activity, and HW appeared as the most effective (IC50 = 0.8 +/- 0.1 mg/ml for HeLa cells). HA proved to be a good 1,1-diphenyl-2-picrylhydrazyl radical scavenger and exhibited the strongest ferric-reducing power (EC50 = 0.07 +/- 0.3 mg/ml). The same extract (HA) also expressed the strongest ferric-reducing power (EC50 = 0.99 +/- 0.1 mg/ml). Hot alkali extraction contributed significantly to ACE inhibitory activity (EC50 = 0.06 +/- 0.00 mg/ml) and to antimicrobial activity, especially against highly resistant Enterococcus faecalis (minimum inhibitory concentration: 0.156 +/- 0.000 mg/ml; and minimum bactericidal concentration: 1.25 +/- 0.00 mg/ml).

Series of twelve chalcone and propafenone derivatives has been synthesized and evaluated for anticancer activities against Hela, Fem-X, PC-3, MCF-7, LS174 and K562 cell lines. The 2D-QSAR and 3D-QSAR studies were performed for all compounds with cytotoxic activities against each cancer cell line. Partial least squares (PLS) regression has been applied for selection of the most relevant molecular descriptors and QSAR models building. Predictive potentials of the created 2D-QSAR and 3D-QSAR models for each cell line were compared, by use of leave-one-out cross-validation and external validation, and optimal QSAR models for each cancer cell line were selected. The QSAR studies have selected the most significant molecular descriptors and pharmacophores of the chalcone and propafenone derivatives and proposed structures of novel chalcone and propafenone derivatives with enhanced anticancer activity on the HeLa, Fem-X, PC-3, MCF-7, LS174 and K562 cells.

Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC(50)s between 42 and 166 mu M) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

Background: The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Cernjavski & Soska (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). Methods: The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results: The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion: Extracts obtained from the endemic plant Helichrysum zivojinii may represent an im

Uvod: Pronalaženje agenasa sa potencijalnim antitumorskim dejstvom je imperativ u modernoj onkologiji. Pri tome se sve više zapaža da određene hemijske strukture imaju specifičnije toksično dejstvo na maligne ćelije. Otkriće artemizinina je označilo početak istraživanja peroksida kao potencijalne zamene za tradicionalne antimalarijske lekove, a iz ovih istraživanja nastala je i strukturno jednostavna klasa peroksida - 1,2,4,5-tetraoksani, za koje je ubrzo pokazano da pored antimalarijskog pokazuju i snažan antiproliferativni efekat. Maligne ćelije imaju poremećaje u regulatornim mehanizmima koji upravljaju ćelijskom proliferacijom i homeostazom. Sposobnost tumorskih ćelijskih populacija da povećaju broj ćelija je određena ne samo intenzitetom ćelijske proliferacije, već i brzinom uklanjanja ćelija. Programirana ćelijska smrt - apoptoza, predstavlja glavni izvor ovog uklanjanja. Cilj rada je bio da se odredi nivo citotoksičnog dejstva grupe mešovitih tetraoksana prema različitim humanim malignim ćelijama, kao i da se odredi koeficijenat selektivnosti u njihovom dejstvu u odnosu na zdrave imunokompetentne ćelije. U cilju dobijanja uvida u mehanizam dejstva ispitivanih jedinjenja odrediće se tip ćelijske smrti koju indukuju ispitivani tetraoksani, kao i produkcija reaktivnih kiseoničnih vrsta u Hela ćelijama. Cilj 3D QSAR studije o antiproliferativoj aktivnosti trideset tri 1,2,4,5-tetraoksanska derivata prema Hela i Fem-x tumorskim ćelijskim linijama, je bio da se utvrdi koje su najvažnije farmakofore steroidnih tetraoksana koje utiču na potenciju ispitivanih jedinjenja prema HeLa i Fem-x tumorskim ćelijskim linijama. Materijal i metode: Citotoksično dejstvo tetraoksana DO-122 - DO-124 i DO-126 - DO-128, prema pet tumorskih ćelijskih linija je ispitivano standardnim MTT testom. U cilju određivanja tipa ćelijske smrti indukovane tretmanom ispitivanim tetraoksanima načinjena je morfološka analiza HeLa ćelija obojenih smešom akridin oranža i etidijum bromida. Analiza odr

Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted. © 2011 Elsevier Masson SAS. All rights reserved.

An alignment-free 3D QSAR study on antiproliferative activity of the thirty-three 1,2,4,5-tetraoxane derivatives toward two human dedifferentiated cell lines was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), were used It was found that pharmacophoric pattern attributed to the most potent derivatives Include amido NH of the primary or secondary amide, and the acetoxy fragments at positions 7 and 12 of steroid core which are, along with the tetraoxane ring, common for all studied compounds. Independently, simple multiple regression model obtained by using the whole-molecular properties, confirmed that the hydrophobicity and the H-bond donor properties are the main parameters influencing potency of compounds toward human cervix carcinoma (HeLa) and human malignant melanoma (FemX) cell lines Corollary, similar structural motifs are found to be Important for the potency toward both examined cell lines. (C) 2010 Elsevier Masson SAS. All rights reserved.

Red and white wine polyphenols have been reported to provide substantial health benefits. In this study, the cytotoxic activity of red and white wine polyphenolic extracts and of resveratrol was evaluated against different cancer cell lines-human cervix adenocarcinoma HeLa, human breast adenocarcinoma MDA-MB-361, and human breast carcinoma MDA-MB-453 and normal human peripheral blood mononuclear cells (PBMCs). Qualitative and quantitative compositions of wine polyphenolic extracts obtained by fractional vacuum distillation of corresponding wines were determined using spectrophotometric methods and high-performance liquid chromatography with diode array detection and liquid chromatography with electrospray ionization-time of flight mass spectrometry analysis. It was demonstrated that wine polyphenolic extracts and resveratrol exerted higher cytotoxic activity against HeLa and MDA-MB-453 cells in comparison to MDA-MB-361 cells and unstimulated and stimulated PBMCs. Furthermore, white wine polyphenolic extract exhibited a significantly higher antiproliferative action on cancer cell lines than red wine extract. The presence of condensed or fragmented nuclei in HeLa cells, pretreated with extract of white wine and stained with a mixture of acridine orange and ethidium bromide, pointed to the morphological signs of apoptosis. In addition, HeLa cells in late stages of apoptosis or secondary necrosis were also observed. Results from our study suggest that polyphenolic extracts from red and white wine may have anticarcinogenic potential.

Dehydroxylated MCM-41 and SBA-15 surfaces were modified by the grafting of two different titanocene complexes ([Ti(Tη5-C5H 4Me)2Cl2] and [Ti(Me2Si(η 5-C5Me4) (η5-C5H 4)}Cl2]) to give new materials, which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, MAS-NMR spectroscopy, thermogravimetry, SEM, and TEM. The toxicity of the resulting materials toward human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells, such as peripheral blood mononuclear cells PBMC has been studied. Estimation of the number of particles per gram of material led to the calculation of O 50 values for these samples, which is the number of particles required to inhibit normal cell growth by 50%. In addition, M50 values (quantity of material needed to inhibit normal cell growth by 50%) of the studied surfaces is also reported. Nonfunctionalized MCM-41 and SBA-15 did not show notable antiproliferative activity, whereas functionalization of these materials with different titanocene based anticancer drugs led to very promising antitumoral activity. The best Q50 values correspond to titanocene functionalized MCM-41 surfaces (MCM-41/[Ti(η5C5H 4Me)2Cl2] (1) and MCM-41/[TiIMe 2Si(Tf-C5Me4)(Tf-C5H 4)(Cl2] (2)) with Q50 values between 3.8 ± 0.6 x 108 and 24.5 ±3.0 x 108 particles. Titanocene functionalized SBA-15 surfaces (SBA-15/[Ti(η5-C 5H4Me)2Cl2] (3) and SBA-15/[Ti{Me2Si(η5-C5Me 4)(η5C5H4)}Cl2] (4)) gave higher Q50 values, showing lower activity from 73.2 ± 9.9 x 108 to 362±7×l08 particles. The best response of the studied materials in terms of M50 values was observed against Fem-x (309 ± 42 g for 4) and K562 (338±18 g for 2), whereas moderate activities were observed in HeLa cells (from 508±63g of 2 to 912 ± 10g of 1). In addition, the analyzed surfaces presented only marginal activity against unstimulated and stimulated PBMC, showing a slight selectivity on human cancer cells. Comparison

Phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent result in the formation of ,-unsaturated carboxylic acids. The reaction was performed at room temperature for 24h. The corresponding conjugated acids were obtained from cyclic or aromatic ketones, whereas bromo acids were obtained from 4-oxo-piperidine-1- carboxylic acid ethyl ester (13) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14).

New R2eddip-type esters (R = cyclopentyl, L3·2HCl 1.5H2O; cyclohexyl, L4·2HCl·H2O) and corresponding palladium(II) complexes, [PdCl2L3] (3) and [PdCl2L4]·H2O (4), as well as [PdCl2L2] (2; L2 diisobutyl ester of eddip) were synthesized and characterized by IR, 1H and 13C NMR spectroscopies and elemental analysis. The crystal structure of L3·2HCl·2CHCl3 was resolved and is given herein. The NMR spectroscopy confirmed the presence of two isomers (from three possible) for each palladium(II) complex. DFT calculations support the formation of two diastereoisomers. In addition, antitumoral investigations were performed and these investigations also included the diisopropyl ester of eddip (L1) and corresponding palladium(II) complex, [PdCl2L1] (1). In vitro antiproliferative activity was determined against several tumor cell lines HeLa, Fem-x, K562 and rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear cells -PBMCs) using MTT test.

A simple approach to a stable steroidal estrone derived A,B-spiro system is reported. Treatment of estrone derived A-ring diepoxyalcohol with the Ac2O-TMSOTf system at the ambient temperature led to acetylation, while at the reflux temperature the acid-catalysed rearrangement took place affording the spiro-compound. Results of extensive in vitro and in vivo anticancer tests on the diepoxide, as well as preliminary data on the antiproliferative activity of the spiro-product against three cancer cell lines, are also presented.

New R(2)eddip-type esters (R = cyclopentyl, L3 center dot 2HCl 1.5H(2)O; cyclohexyl, L4 center dot 2HCl center dot H2O) and corresponding palladium(II) complexes, [PdCl(2)L3] (3) and [PdCl2L4]center dot H2O (4), as well as [PdCl2L2] (2: L2 diisobutyl ester of eddip) were synthesized and characterized by IR, H-1 and C-13 NMR spectroscopies and elemental analysis. The crystal structure of L3 center dot 2HCl center dot 2CHCl(3) was resolved and is given herein. The NMR spectroscopy confirmed the presence of two isomers (from three possible) for each palladium(II) complex. DFT calculations support the formation of two diastereoisomers. In addition, antitumoral investigations were performed and these investigations also included the diisopropyl ester of eddip (L1) and corresponding palladium(II) complex, [PdCl(2)L1] (1). In vitro anti proliferative activity was determined against several tumor cell lines HeLa, Fem-x, K562 and rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear cells -PBMCs) using MTT test. (C) 2009 Elsevier Masson SAS. All rights reserved.

Phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent result in the formation of alpha,beta-unsaturated carboxylic acids. The reaction was performed at room temperature for 24h. The corresponding conjugated acids were obtained from cyclic or aromatic ketones, whereas bromo acids were obtained from 4-oxo-piperidine-1-carboxylic acid ethyl ester (13) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14).

In this study we investigated the antiproliferative activity of six mixed steroidal tetraoxanes against various tumor cell lines, the toxicity against normal peripheral blood mononuclear cells (PBMC), and the mode of HeLa cell death induced by these compounds. Investigated tetraoxanes exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HeLa cells for 24 h with all tetraoxanes induced apoptosis, as confirmed by morphological analysis and by the appearance of a typical ladder pattern in the DNA fragmentation assay.

Ruthenium(III) complexes formulated as K2[Ru(sar)Cl4]H2O and K[Ru(dmgly)2Cl2]3H2O containing bidentate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dmgly) as well as K[Ru(pdda)Cl2]2.5H2O complex with tetradentate 1,3-propylenediamine-N,N'-diacetato were synthesized. The complexes were obtained by direct reaction of ruthenium(III) chloride with the corresponding bidentate or tetradentate ligand followed by addition of a base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. To assess selectivity in the antitumor action of these complexes, their antiproliferative activities against human adenocarcinoma HeLa cells, human myelogenous leukemia K562 cells, human breast carcinoma MDA-MB-361 and MDA-MB-453 cells and normal immunocompetent PBM cells were determined.

Two new p-cymene ruthenium(II) complexes containing as additional ligands N-methylpiperazine ([(eta(6)-p-cymene)RuCl2(CH3NH(CH2)(4)NH)]PF6, complex 1) or vitamin K-3-thiosemicarbazone ([(eta(6)-p-cymene)RuCl2(K(3)tsc)], complex 2) were synthesized starting from [(eta(6)-p-cymene)(2)RuCl2](2) and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed "piano-stool" geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present., Sintetisana su dva nova p-cimen-rutenijum(II) kompleksa koji sadrže kao dodatne ligande N-metilpiperazin ([(h6-p-cimen)RuCl2(CH3NH(CH2)4NH)]PF6, kompleks 1) i vitamin K3-tiosemikarbazon ([(h6-p-cimen)RuCl2(K3tsc)], kompleks 2). Oba nova kompleksa dobijena su polazeći od [(h6-p-cimen)2RuCl2]2 kompleksa i odgovarajućeg liganda. Kompleksi su okarakterisani elementalnom analizom, IC, elektronsko-apsorpcionom i NMR spektroskopijom. Rendgeno-strukturna analiza kompleksa 1 pokazala je “piano-stool” geometriju. U zavisnosti od prisutnog liganda diskutovana je razlika u citotoksičnoj aktivnosti ova dva dobijena kompleksa.

Article describes the synthesis of fifteen β-hydroxy- β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2- bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC 50 values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4-biphenylyl)-butanoic acid, having the IC 50 value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC 50 > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity.

The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined.

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9 11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9 alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound. (c) 2006 Elsevier Ltd. All rights reserved.

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9 11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9 alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound. (c) 2006 Elsevier Ltd. All rights reserved.

The antitumour action of three polyoxometallate compounds of Keggin's type: 12-molibdophosphoric acid (MoPA), 12-tungstophosphoric acid (WPA) and Mg salt of WPA (MgHWPA) was studied in vitro. For human cervix carcinoma (HeLa) cells survival, as well as for nonstimulated and stimulated peripheral blood mononuclear cells (PBMC), MTT test was applied and IC50 values of POMs were determinated. Index selectivity for WPA and MgHWPA are 1.9 and 1.8, calculated for nonstimulated, as well as 2.5 and 2.0, calculated for stimulated PBMS. Combination of studied POMs do not contribute to their lower IC50 values. Apoptosis detection implies mild cytotoxic effect of WPA and more cytostatical effect of MgHWPA. Combination of each of the studied POMs with caffeine decreases HeLa survival in dose dependent way. None of the studied POMs in the used concentrations (up to 100 mmol/L) damages blood cells and/or decreases their number., Ispitivano je in vitro antitumorsko dejstvo tri jedinjenja iz grupe polioksometalata (POM-a) Keginovog tipa: 12-fosformolibdenska kiselina (MoPA), 12-fosforvolframova kiselina (WPA) i Mg so 12-fosforvolframove kiseline (MgHWPA). Primenom MTT testa na ćelije karcinoma cerviksa (HeLa ćelije), kao i na nestimulisane i stimulisane mononuklearne ćelije iz periferne krvi (PBMC), određene su IC50 vrednosti ispitivanih POM-a. Indeksi selektivnosti za WPA i MgHWPA su 1,9 i 1,8 računati za nestimulisane, odnosno 2,5 i 2,0 za stimulisane PBMC. Kombinacijom ispitivanih POMa ne postiže se smanjenje njihovih IC50 vrednosti. Detekcijom apoptoze utvrđeno je da WPA pokazuje blagi citotoksični efekat, dok MgHWPA ima blagi citotostatski efekat. U kombinaciji sa kofeinom, POM jedinjenja još više smanjuju preživljavanje HeLa ćelija. U ispitivanim koncentracijama (do 100 mmol/L), nijedno od POM jedinjenja ne utiče na broj i izgled krvnih ćelija pune krvi zdravih davalaca.

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.