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Growth Inhibitory Activity (growth + inhibitory_activity)
Selected AbstractsSuppression of anti- Candida activity of macrophages by a quorum-sensing molecule, farnesol, through induction of oxidative stressMICROBIOLOGY AND IMMUNOLOGY, Issue 6 2009Shigeru Abe ABSTRACT Farnesol is well known as a quorum-sensing molecule of Candida albicans. To assess the pathological function of farnesol, its effects on macrophage viability and functions including growth inhibitory activities against C. albicans were examined in vitro. Murine macrophages, when cultured in the presence of 56,112 ,M of farnesol for 1,2 hr, decreased their activity inhibiting the mycelial growth of C. albicans and lost their viability. This suppression of macrophage function by farnesol was neutralized by the coexistence of the anti-oxidants probucol and trolox. Macrophages cultured in the presence of farnesol for 2 hr displayed morphological change of nuclei and DNA fragmentation, which suggested apoptosis of the cells. Intracellular production of ROS in the farnesol-treated macrophages was shown by fluorescence of DCFH-DA and increase of peroxidized materials. These effects of farnesol were blocked by probucol or trolox. These results indicate that farnesol lowered viability of the murine macrophages and suppressed their anti- Candida activity, perhaps through induction of ROS. [source] Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell linesPHYTOTHERAPY RESEARCH, Issue 5 2009Boglárka Csupor-Löffler Abstract The antiproliferative activities of n -hexane, chloroform, aqueous-methanol and aqueous extracts of the aerial parts of the Achillea millefolium aggregate on three human tumour cell lines were investigated by means of MTT assays. The chloroform-soluble extract exerted high tumour cell proliferation inhibitory activities on HeLa and MCF-7 cells, and a moderate effect on A431 cells; accordingly, it was subjected to detailed bioactivity-guided fractionation. As a result of the multistep chromatographic purifications (VLC, CPC, PLC, gel filtration), five flavonoids (apigenin, luteolin, centaureidin, casticin and artemetin) and five sesquiterpenoids (paulitin, isopaulitin, psilostachyin C, desacetylmatricarin and sintenin) were isolated and identified by spectroscopic methods. The antiproliferative assay demonstrated that centaureidin is the most effective constituent of the aerial parts of yarrow: high cell growth inhibitory activities were observed especially on HeLa (IC50 0.0819 µm) and MCF-7 (IC50 0.1250 µm) cells. Casticin and paulitin were also highly effective against all three tumour cell lines (IC50 1.286,4.76 µm), while apigenin, luteolin and isopaulitin proved to be moderately active (IC50 6.95,32.88 µm). Artemetin, psilostachyin C, desacetylmatricarin and sintenin did not display antiproliferative effects against these cell lines. This is the first report on the occurrence of seco -pseudoguaianolides (paulitin, isopaulitin and psilostachyin C) in the Achillea genus. Copyright © 2008 John Wiley & Sons, Ltd. [source] Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabineDRUG DEVELOPMENT RESEARCH, Issue 5 2010Rosario Pignatello Abstract Lipophilic derivatives of the antitumor drug gemcitabine (GEM) with the potential for improving drug loading in lipid-based colloidal carriers, like liposomes or lipid nanoparticles, are described. GEM free base was conjugated to lipoamino acids bearing an alkyl side chain of different length, by either a carbodiimide-assisted or an ethylchloroformiate-assisted coupling reaction, to obtain N4 -acyl GEM derivatives. These compounds retained the same in vitro cell growth inhibitory activity of the parent drug against two lines of human anaplastic thyroid cancer cells. Stability studies suggested that the observed activity was due mainly to intact derivatives and not to released GEM. Accordingly, these amphiphilic derivatives can be proposed in a further step for the encapsulation in liposomes or lipid nanocarriers, to achieve as a final goal an improvement of the pharmacokinetics and therapeutic activity of GEM. Drug Dev Res 2010. © 2010 Wiley-Liss, Inc. [source] Secondary Metabolites from the Fungus Chaetomium brasilienseHELVETICA CHIMICA ACTA, Issue 1 2008Guo-You Li Abstract Two new depsidones, mollicellins I and J (1 and 2, resp.), and a new chromone, 2-(hydroxymethyl)-6-methylmethyleugenin (3), along with six known compounds, 4,9, were isolated from the ethyl acetate extract of a solid-state fermented culture of Chaetomium brasiliense. Their structures were elucidated based on spectroscopic analysis. Mollicellins I and H (5) exhibited significant growth inhibitory activity against human breast cancer (Bre04), human lung (Lu04), and human neuroma (N04) cell lines with GI50 values between 2.5,8.6,,g/ml. [source] Activity and mode of action against fungal phytopathogens of bovine lactoferricin-derived peptidesJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2006A. Muñoz Abstract Aim:, To evaluate the activity against fungal phytopathogens of two synthetic peptides derived from the protein bovine lactoferricin: the antibacterial active core of six amino acid residues (LfcinB20,25) and an extension of 15 amino acids (LfcinB17,31). Methods and Results:,In vitro activity against fungal pathogens was determined and compared with that against model micro-organisms. Activity was demonstrated against fungi of agronomic relevance. Distinct antimicrobial properties in vitro were found for the two peptides. LfcinB17,31 had growth inhibitory activity higher than LfcinB20,25. However, LfcinB17,31 was not fungicidal to quiescent conidia of Penicillium digitatum at the concentrations assayed, while LfcinB20,25 killed conidia more efficiently. Microscopical observations showed that the mycelium of P. digitatum treated with LfcinB17,31 developed alterations of growth, sporulation and chitin deposition, and permeation of hyphal cells. In experimental inoculations of mandarins, both peptides showed limited protective effect against the disease caused by P. digitatum. Conclusions:, LfcinB20,25 and LfcinB17,31 peptides were shown to have antimicrobial activity against plant pathogenic filamentous fungi, with distinct properties and mode of action. Significance and Impact of the Study:, LfcinB20,25 and LfcinB17,31 peptides offer novel alternatives to develop resistant plants by molecular breeding. [source] Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-,36JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Lianguo Kang Abstract The dietary isothiocyanates (ITCs) exhibit strong chemopreventive activities for a variety of neoplasms including breast cancer. However, the molecular mechanisms underlying ITC function in breast cancer cells have not been well established. Here, we found that phenethyl isothiocyanate (PEITC) acted more potently than the ,pure' anti-oestrogen ICI 182,780 to inhibit the growth of oestrogen receptor (ER)+ breast cancer MCF7 and H3396 cells and ER, MDA-MB-231 and SK-BR-3 cells. PEITC reduced the steady state levels of ER-, and its novel variant, ER-,36 in a dose-and time-dependent manner and inhibited oestrogen-induced activation of the mitogen activated protein kinase/ERK 1/2 signaling pathway. However, ICI 182,780 that is potent in destabilization of ER-, protein, failed to down-regulate ER-,36. Our results thus demonstrated that PEITC functions as a more potent ER-,,disruptor' than the well-known ICI 182,780 to abrogate ER-mediated mitogenic oestrogen signaling in breast cancer cells, which provides a molecular explanation for the strong growth inhibitory activity of ITCs in breast cancer cells, and a rational for further exploration of ITCs as chemopreventive agents for human mammary carcinogenesis. [source] Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel Inhibit growth of human lung cancer cells by apoptosisMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 3 2009Hang Xiao Abstract Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3,,4,-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3,,4,-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3,,4,-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/G1 phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention. [source] Antiplasmodial and cytotoxic activity of khellactone derivatives from Angelica purpuraefolia chungPHYTOTHERAPY RESEARCH, Issue 3 2010Ill-Min Chung Abstract The methanolic extract of the rhizomes parts of Agelica purpuraefolia was investigated for its activity against chloroquine-sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two natural khellactone, (+)-4,-Decanoyl- cis -khellactone (1) and (+)-3,-Decanoyl- cis -khellactone (2) were isolated from the rhizomes parts of A. purpuraefolia. Two compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK-OV-3 cancer cell line cells. Compounds 1, 2 showed notable growth inhibitory activity against chloroquine-sensitive strains of Plasmodium falciparum with IC50 values from 1.5 and 2.4,,M. This compound showed no significant cytotoxicity (IC50 > 100,,M) evaluated using SK-OV-3 cancer cell line cells. This is the first report on the antiplasmodial activity of the compounds from A. purpuraefolia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Facile Synthesis and In-Vitro Antitumor Activity of Some Pyrazolo[3,4- b]pyridines and Pyrazolo[1,5- a]pyrimidines Linked to a Thiazolo[3,2- a]benzimidazole MoietyARCHIV DER PHARMAZIE, Issue 1 2010Hatem A. Abdel-Aziz Abstract The key precursor E -3-(N,N -dimethylamino)-1-(3-methylthiazolo[3,2- a]benzimidazol-2-yl)prop-2-en-1-one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5-amino-3-aryl-1 - phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4- b]pyridines 7a, b. Similarly, pyrazolo[1,5- a]pyrimidines 10a, b and 14a,f were prepared by reaction of enaminone 4 with 5-amino-1H -pyrazoles 8a, b and 12a,f, respectively. The structure of pyrazolo[1,5- a]pyrimidine 10b was determined by X-ray diffraction. The synthesized compounds were tested for their in-vitro antitumor activity against the colon cancer cell line CaCo-2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo-2 cell line (IC50 = 0.5 ,g/mL) was coupled with a lower toxicity against BHK (IC50 = 2.3 ,g/mL). [source] Triterpenoid Alkaloids from Buxus microphyllaCHEMISTRY & BIODIVERSITY, Issue 7 2010Yu-Xin Yan Abstract Two new triterpenoid alkaloids, buxmicrophyllines J and K (1 and 2, resp.), together with four analogues, 3,6, were isolated from the leaves and stems of Buxus microphylla. The structures of the new compounds were elucidated by NMR and MS spectroscopic analyses. The partial assignments of the NMR spectra of 3 were also revised. Compounds 1 and 3,6 were evaluated for their growth inhibitory activity against human cell lines HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1. Compound 6 showed significant cytotoxicity against HL-60, SK-BR-3, and PANC-1 cell lines, with IC50 values of 6.46, 19.61, and 28.57,,M, respectively. [source] Synthesis, Cytotoxicity, and Apoptosis Induction in Human Tumor Cells by Geiparvarin AnaloguesCHEMISTRY & BIODIVERSITY, Issue 9 2004Giampietro Viola A series of geiparvarin analogues modified on the unsaturated alkenyloxy bridge, where a H-atom replaced the 3,-Me group, were synthesized and evaluated against a panel of human tumor cell lines in vitro. These compounds demonstrated a stronger increase in growth inhibitory activity when compared to the parent compound geiparvarin (8). In particular, the activity increased even further in the series of demethylated compounds when a Me substituent in the coumarin moiety is introduced. On the contrary, the same modifications exerted on the parent compound led to an activity reduction. Interestingly, the new derivatives proved to be fully inhibitory to drug-resistant cell lines, thus suggesting that they are not subject to the pump-mediating efflux of antitumor drugs. On the basis of their cytotoxic profiles, the most-active compounds were selected for further biological evaluation. The extracellular acidification rate by the new geiparvarin analogues was measured with the CytosensorTM microphysiometer. The new derivatives significantly increased the acidification rate during the 24,48,h of incubation in a concentration-dependent manner. Cell-cycle analysis, evaluated by flow cytometry, revealed a strong apoptotic induction by these compounds confirmed by DNA laddering and observation by electron microscopy. Interestingly, the apoptotic pathway did not appear to be mediated by the activation of caspase-3. [source] Synthesis and Biological Evaluation of New Geiparvarin DerivativesCHEMMEDCHEM, Issue 5 2009Stefano Chimichi Prof. Abstract New geiparvarin derivatives modified at the alkenyloxy bridge, where the 3,-methyl group was replaced by a hydrogen atom, were synthesized and evaluated against a panel of human tumor cell lines in,vitro. Compounds (R)- 4 and (R)- 5 show greater inhibitory activity toward cell growth than the parent geiparvarin. New geiparvarin derivatives modified at the unsaturated alkenyloxy bridge, where a hydrogen atom replaces the 3,-methyl group, were synthesized and evaluated against a panel of human tumor cell lines in,vitro. These compounds demonstrated an increase in growth inhibitory activity relative to the parent compound, geiparvarin. The activity increased even further in the series of demethylated compounds, with the introduction of a methyl group at the 1,-position of the alkenyloxy chain. In contrast, a remarkable decrease in activity was observed with the introduction of a methyl group at the 2,-position. Interestingly, the new derivatives fully inhibited the growth of drug-resistant cell lines, suggesting that they are not subject to pump-mediated drug efflux. On the basis of their cytotoxic profiles, the most active compounds (R)- 4 and (R)- 5 were selected for further biological evaluation in comparison with the lead compound. The new derivatives strongly induce apoptosis in a promyelocytic leukemia cell line (HL-60) mediated by depolarization of mitochondrial transmembrane potential and mitochondrial production of reactive oxygen species (ROS). [source] | ||||||||||||||||