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Human Tumor Cell Lines (human + tumor_cell_line)
Selected AbstractsAntiproliferative Effect of Furanocoumarins from the Root of Angelica dahurica on Cultured Human Tumor Cell LinesPHYTOTHERAPY RESEARCH, Issue 3 2007Young-Kyoon Kim Abstract A bioassay-guided fractionation of the root extract of Angelica dahurica (Umbelliferae) led to the isolation of six furanocoumarins as active ingredients responsible for the antitumoral property. The hexane soluble part of the extract demonstrated a signicant inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited poor inhibition. Intensive investigation of the hexane soluble part of the extract yielded six furanocoumarins, i.e. isoimperatorin, cnidicin, imperatorin, oxypeucedanin, byakangelicol, oxypeucedanin hydrate, all of which exhibited a signicant inhibition on cell proliferation in a dose-dependent manner. Copyright © 2006 John Wiley & Sons, Ltd. [source] Psoralen Analogues: Synthesis, Inhibitory Activity of Growth of Human Tumor Cell Lines and Computational Studies.CHEMINFORM, Issue 34 2006A. M. A. G. Oliveira Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Centriole separation in DNA damage-induced centrosome amplificationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2009Chiara Saladino Abstract Altered centrosome numbers are seen in tumor cells in response to DNA damaging treatments and are hypothesised to contribute to cancer development. The mechanism by which the centrosome and chromosome cycles become disconnected after DNA damage is not yet clear. Here, we show that centrosome amplification occurs after ionising radiation (IR) in chicken DT40 cells that lack DNA-PK, Ku70, H2AX, Xpa, and Scc1, demonstrating that these activities are not required for centrosome amplification. We show that inhibition of topoisomerase II induces Chk1-dependent centrosome amplification, a similar response to that seen after IR. In the immortalised, nontransformed hTERT-RPE1 line, we observed centriole splitting, followed by dose-dependent centrosome amplification, after IR. We found that IR results in the formation of single, not multiple, daughter centrioles during centrosome amplification in U2OS osteosarcoma cells. Analysis of BRCA1 and BRCA2 mutant tumor cells showed high levels of centriole splitting in the absence of any treatment. IR caused pronounced levels of centrosome amplification in BRCA1 mutant breast cancer cells. These data show that centrosome amplification occurs after different forms of DNA damage in chicken cells, in nontransformed human cells and in human tumor cell lines, indicating that this is a general response to DNA damaging treatments. Together, our data suggest that centriole splitting is a key step in potentiation of the centrosome amplification that is a general response to DNA damage. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Characterization by NMR Spectroscopy, X-ray Analysis and Cytotoxic Activity of the Ruthenium(II) Compounds [RuL3](PF6)2(L = 2-Phenylazopyridine or o -Tolylazopyridine) and [RuL'2L"](PF6)2(L', L" = 2-Phenylazopyridine, 2,2'-Bipyridine)EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 13 2005Anna C. G. Hotze Abstract Tris(ligand) complexes [RuL3](PF6)2 (L = 2-phenylazopyridine or o -tolylazopyridine) and mixed ligand [RuL'2L"](PF6)2 (L' and L" are 2-phenylazopyridine or 2,2'-bipyridine) have been synthesized, structurally characterized and investigated for cytotoxic activity. These complexes are important to study the hypothesis that the compound ,-[Ru(azpy)2Cl2] (azpy = 2-phenylazopyridine) exhibits a high cytotoxicity due to its two cis chloride ligands, which might be exchanged for biological targets as DNA. Molecular structures of mer -[Ru(azpy)3](PF6)2 (1) and mer -[Ru(tazpy)3](PF6)2 (5) (tazpy = o -tolylazopyridine) have been determined by X-ray diffraction. Series of complexes [RuL3](PF6)2 and [RuL'2L"](PF6)2 show interesting NMR spectroscopic data; e.g. the spectrum of mer -[Ru(azpy)3](PF6)2 (1) shows extremely broadened resonances at room temp. but sharpened resonances at low temperature. In the 1H NMR spectra of compounds [Ru(azpy)2(bpy)]2+ and [Ru(bpy)2(azpy)]2+ (bpy = 2,2-bipyridine), respectively, less broadened (room temp.) or completely sharp resonances (room temp.) occur in comparison to 1 (under same conditions). By selecting the right temperature and/or concentration, NMR spectra of these series of compounds have been resolved using 2D COSY and NOESY NMR spectroscopy. Remarkably, the cytotoxicity data against a series of human tumor cell lines (A498, EVSA-T, H226, IGROV, M19, MCF-7 and WIDR) show a moderate cytotoxicity for these series of tris(ligand) complexes. So, even though no chloride ligands are present in these tris(ligand) complexes, a considerable cytotoxic activity is observed. This would imply that the 2-phenylazopyridine ruthenium(II) complexes act by a completely different mechanism than the well-known cisplatin. This finding is important, because an anticancer compound acting via a different mechanism is a prerequisite in designing new anticancer drugs. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Trichocladinols A,C, Cytotoxic Metabolites from a Cordyceps -Colonizing Ascomycete Trichocladium opacumEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 32 2009Huijuan Guo Abstract Trichocladinols A,C (1,3), three new metabolites, and the known massarigenin A (4), have been isolated from cultures of a Cordyceps -colonizing ascomycete Trichocladium opacum. Their structures were elucidated by NMR spectroscopy and X-ray crystallography. The absolute configuration of 1 was assigned by using the modified Mosher method and that of 3 was determined by X-ray crystallographic analysis of its (S)-MTPA ester. Compounds 1,3 showed modest cytotoxic effects against the human tumor cell lines HeLa and MCF-7. Structurally, compounds 1 and 2 possess a previously undescribed 2,9-dioxatricyclo[5.2.1.03,8]dec-4-ene skeleton.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Apralactone A and a New Stereochemical Class of Curvularins from the Marine Fungus Curvularia sp.EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 30 2008Hendrik Greve Abstract Chemical investigations of the cytotoxic extract of the marine fungus Curvularia sp. (strain no. 768), isolated from the red alga Acanthophora spicifera, yielded the novel macrolide apralactone A (1), as well as the antipodes of curvularin macrolides 2,7. Compound 8, a dimeric curvularin was recognised as an artefact. The structures of 1,8 were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, CD, MS, UV and IR). Apralactone A (1) is a 14-membered phenyl acetic acid macrolactone, and the first such compound with a 4-chromanone substructure. Compounds 1, 2, 4, 5 and 6 were found to be cytotoxic towards human tumor cell lines with mean IC50 values in the range of 1.25 to 30.06 ,M. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Suppression of cyclic GMP-specific phosphodiesterase 5 promotes apoptosis and inhibits growth in HT29 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Bing Zhu Abstract Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Here, we demonstrate that suppression of PDE5 gene expression by antisense pZeoSV2/ASP5 plasmid transfection results in a sustained increase in [cGMP]i, growth inhibition, and apoptosis in human colon tumor HT29 cells. With stable transfection, antisense transcripts exhibited a specific suppression in PDE5 activity, mRNA levels, and a 93 kDa hPDE5A1 protein. In cloned antisense cells, prolongation of the cell growth doubling times correlate positively with suppressed PDE5 activity and increased [cGMP]i. The growth inhibition in PDE5 antisense clones is due to an increased apoptotic rate and delayed cell-cycle progression. These results corroborate previous findings with the PDE5 inhibitor exisulind and its derivatives showing that sustained [cGMP]i induces apoptosis and growth inhibition in tumor cells. Furthermore, an inducible mitotic inhibitor p21WAF1/CIP1 has been found to account for the delay of cell-cycle progression in PDE5 antisense clones at G2/M phase. A proteolytic cleavage of p21WAF1/CIP1 in the antisense clones is also increased at the later stage of serum stimulation. The protein kinase G (PKG) inhibitor, KT5823, can prevent the cleavage of p21WAF1/CIP. These data substantiate a pivotal role for PDE5 as a modulator of apoptosis and cell-cycle progression for human carcinoma via a mechanism involving the activation of [cGMP]i/PKG signaling pathways. © 2004 Wiley-Liss, Inc. [source] Characterization of p21Ras -mediated apoptosis induced by protein kinase C inhibition and application to human tumor cell linesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004James S. Liou Suppression of PKC activity can selectively induce apoptosis in cells expressing a constitutively activated p21Ras protein. We demonstrate that continued expression of p21Ras activity is required in PKC-mediated apoptosis because farnesyltransferase inhibitors abrogated the loss of viability in p21Ras -transformed cells occurring following PKC inhibition. Studies utilizing gene transfer or viral vectors demonstrate that transient expression of oncogenic p21Ras activity is sufficient for induction of apoptosis by PKC inhibition, whereas physiologic activation of p21Ras by growth factor is not sufficient to induce apoptosis. Mechanistically, the p21Ras -mediated apoptosis induced by PKC inhibition is dependent upon mitochondrial dysregulation, with a concurrent loss of mitochondrial membrane potential (,m). Cyclosporine A, which prevented the loss of ,m, also inhibited HMG-induced DNA fragmentation in cells expressing an activated p21Ras. Induction of apoptosis by PKC inhibition in human tumors with oncogenic p21Ras mutations was demonstrated. Inhibition of PKC caused increased apoptosis in MIA-PaCa-2, a human pancreatic tumor line containing a mutated Ki,ras allele, when compared to HS766T, a human pancreatic tumor line with normal Ki,ras alleles. Furthermore, PKC inhibition induced apoptosis in HCT116, a human colorectal tumor line containing an oncogenic Ki,ras allele but not in a subline (Hke3) in which the mutated Ki,ras allele had been disrupted. The PKC inhibitor 1- O -hexadecyl-2- O -methyl-rac-glycerol (HMG), significantly reduced p21Ras -mediated tumor growth in vivo in a nude mouse MIA-PaCa-2 xenograft model. Collectively these studies suggest the therapeutic feasibility of targeting PKC activity in tumors expressing an activated p21Ras oncoprotein. J. Cell. Physiol. 198: 277,294, 2004. © 2003 Wiley-Liss, Inc. [source] Synthesis and antiproliferative evaluation of new aryl substituted pyrido[3,,2,:5,6]thiopyrano[4,3- c]pyrazolesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 7 2005G. Primofiore The preparation and the cytotoxic properties of new derivatives of the planar pyrido[3,,2,:5,6]thiopyrano-[4,3- c]pyrazole system, carrying an arylic side group in the 1 or 2 positions, are described. The novel substituted derivatives were obtained by reaction of suitable arylhydrazines with the appropriate key intermediate 3-hydroxymethylene-2,3-dihydrothiopyrano[2,3- b]pyridin-4(4H)-ones. Moreover the preparation was reported of the 2-carboxamidophenyl derivatives, which was accomplished from the previously obtained pyrido[3,,2,:5,6]thiopyrano[4,3- c]pyrazole nucleus, by reaction with phenylisocyanate. All the new compounds were evaluated for their antiproliferative ability, by an in vitro assay on human tumor cell lines (HL-60 and HeLa). [source] Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studiesMEDICINAL RESEARCH REVIEWS, Issue 3 2010Stefania Nobili Abstract Gold compounds are a class of metallodrugs with great potential for cancer treatment. During the last two decades, a large variety of gold(I) and gold(III) compounds are reported to possess relevant antiproliferative properties in vitro against selected human tumor cell lines, qualifying themselves as excellent candidates for further pharmacological evaluation. The unique chemical properties of the gold center confer very interesting and innovative pharmacological profiles to gold-based metallodrugs. The primary goal of this review is to define the state of the art of preclinical studies on anticancer gold compounds, carried out either in vitro or in vivo. The available investigations of anticancer gold compounds are analyzed in detail, and particular attention is devoted to underlying molecular mechanisms. Notably, a few biophysical studies reveal that the interactions of cytotoxic gold compounds with DNA are generally far weaker than those of platinum drugs, implying the occurrence of a substantially different mode of action. A variety of alternative mechanisms were thus proposed, of which those involving either direct mitochondrial damage or proteasome inhibition or modulation of specific kinases are now highly credited. The overall perspectives on the development of gold compounds as effective anticancer drugs with an innovative mechanism of action are critically discussed on the basis of the available experimental evidence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 3, 550,580, 2010 [source] In vitro antiproliferative effect of six Salvia species on human tumor cell linesPHYTOTHERAPY RESEARCH, Issue 8 2006Giovina Fiore Abstract This study was designed to examine the in vitro antiproliferative activity of the methanol crude extracts of six Salvia species: Salvia dominica L. leaves, Salvia lanigera Desf. aerial parts, Salvia menthaefolia Ten. roots, Salvia palaestina Benth. aerial parts, Salvia sclarea L. roots and Salvia spinosa L. aerial parts. Extracts were screened for their possible antitumoral activity by MTT test on nine human cancer cell lines: glioblastoma (DBTRG-05MG, T98G, U-87MG), colorectal adenocarcinoma (WiDr and HT-29), prostate adenocarcinoma (MDA Pca2b), choriocarcinoma (JEG-3), endometrium adenocarcinoma (HEC-1A) and B lymphoblast (CIR). IC50 values were determined for only five extracts and ranged from 90 to 400 mg/mL approximately. Salvia menthaefolia extract exhibited marked antiproliferative activity against all tumor cell lines showing lower IC50 values, while S. spinosa, S. sclarea and S. dominica extracts showed a degree cytotoxic activity dependent on the cell line type. Finally S. palaestina extract revealed a moderate antiproliferative effect only against three cell lines. Salvia lanigera extract displayed toxic activity at all concentrations tested. The results strengthen the evidence that the genus Salvia could be considered a natural resource of potential antitumor agents. Copyright © 2006 John Wiley & Sons, Ltd. [source] In Vitro culture studies of FlorEssence® on human tumor cell linesPHYTOTHERAPY RESEARCH, Issue 2 2005Joseph Tai Abstract FlorEssence® (FE) is an herbal tea widely used by patients to treat chronic conditions in North America, particularly cancer patients during chemo- and radiation therapy. Although individual components of FE have antioxidant, antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of anticancer activity for the herbal tea itself is still lacking. We studied the antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the proliferation of both breast and leukemia cells in vitro only at high concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20 dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells, with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells showed a significantly increased Sub G0[sol ]G1 fraction after treatment with 1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7 and MDA-MB-468 breast cancer cells were treated with a combination of FE with either paclitaxel or cisplatin, results showed that only the combination of 1[sol ]20 dilution of FE with 0.5 µM cisplatin resulted in a small but significantly higher MCF7 cell survival than 0.5 µM cisplatin treatment alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the antiproliferative properties of these two commonly used chemotherapeutic agents. The results suggest that FE at high concentrations show differential inhibitory effect on different human cancer cell lines. Further studies are needed to assess the biological activities of FE. Copyright © 2005 John Wiley & Sons, Ltd. [source] RD114-pseudotyped retroviral vectors kill cancer cells by syncytium formation and enhance the cytotoxic effect of the TK/GCV gene therapy strategyTHE JOURNAL OF GENE MEDICINE, Issue 4 2005E. Germain Abstract Background Wild-type RD114 virus is capable of generating syncytia during its replication, and it is believed that cell-free viruses direct the fusion of neighboring cells. The RD114 envelope (Env) that mediates this fusion event is now widely used to pseudotype retroviral and lentiviral vectors in gene therapy. Indeed, vectors pseudotyped with RD114 Env are very efficient to transfer genes into human hematopoietic cells, and they are resistant to human complement inactivation. In this study, we have tested the potential of RD114-pseudotyped vectors produced from the FLYRD18 packaging cell line to induce syncytia. Methods RD114-pseudotyped vectors produced from the FLYRD18 packaging cells were added on tumor cell lines, and the formation of syncytia was assessed by microscopy after cell fixation and methylene blue staining. The kinetics of syncytium formation was analyzed by time-lapse microscopy. Finally, the cytotoxic effect of RD114-pseudotyped vectors was measured by the MTT assay on tumor cells, and in combination with the TK/GCV strategy. Results We have found that these vectors were able to mediate cell-to-cell fusion of human tumor cell lines. A few hours after addition of the vector, cells started to aggregate to form syncytia that eventually evolved toward cell death 48 h postinfection. RD114-pseudotyped vectors were very efficient at killing human cancer cells, and they were also able to enhance dramatically the cytotoxic effect of the TK/GCV strategy. Conclusions These findings indicate that RD114-pseudotyped vectors used alone, or in combination with a suicide gene therapy approach, have great potential for the treatment of cancer. Copyright © 2004 John Wiley & Sons, Ltd. [source] Synthesis, characterization and biological studies of alkenyl-substituted titanocene(IV) carboxylate complexesAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 9 2010Goran N. Kalu, erovi Abstract The carboxylate compounds [Ti(,5 -C5H5)(,5 -C5H4{CMe2(CH2CH2CHCH2)})(O2CCH2SXyl)2] (2; Xyl = 3,5-Me2C6H3) and [Ti(,5 -C5H5)(,5 -C5H4{CMe2(CH2CH2CHCH2)})(O2CCH2SMesl)2] (3; Mes 1 = 2,4,6-Me3C6H2) were synthesized by the reaction of [Ti(,5 -C5H5)(,5 -C5H4{CMe2(CH2CH2CHCH2)})Cl2] (1) with 2 equivalents of xylylthioacetic acid or mesitylthioacetic acid, respectively. Compounds 2 and 3 were characterized by spectroscopic methods. The cytotoxic activity of 1,3 was tested against human tumor cell lines from four different histogenic origins,8505C (anaplastic thyroid cancer), DLD-1 (colon cancer) and the cisplatin sensitive A253 (head and neck cancer) and A549 (lung carcinoma),and compared with those of the reference complex [Ti(,5 -C5H5)2Cl2] (R1) and cisplatin. Surprisingly, the cytotoxic activities of the carboxylate derivatives were lower than those of their corresponding dichloride analogue (1). However, complexes 1,3 were more active than titanocene dichloride against all the studied cells with the exception of complex 2 against A253 and A549 cell lines. DNA-interaction tests were also carried out. Solutions of all the studied complexes were treated with different concentrations of fish sperm DNA, observing modifications of the UV spectra with intrinsic binding constants of 2.99 × 105, 2.45 × 105, and 2.35 × 105M,1 for 1,3. Structural studies based on density functional theory calculations of 2 and 3 were also carried out. Copyright © 2010 John Wiley & Sons, Ltd. [source] Synthesis, structural characterization and cytotoxic activity of diorganotin(IV) complexes of N -(5-halosalicylidene)tryptophaneAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 1 2009Laijin Tian Abstract Four new diorganotin(IV) complexes of N -(5-halosalicylidene)tryptophane, R2Sn[5-X-2-OC6H3CHNCH(CH2Ind)COO] [Ind = 3-indolyl; R, X = Et, Cl (1); Et, Br(2); n -Bu, Cl (3); n -Bu, Br (4)], were synthesized and characterized by elemental analysis, IR and NMR (1H, 13C and 119Sn) spectra. The crystal structures of complexes 1,3 were determined by X-ray single crystal diffraction and showed that the tin atoms are in a distorted trigonal bipyramidal geometry and form five- and six-membered chelate rings with the tridentate ligand. Intermolecular weak interactions in 1,3 link molecules, respectively, into a two-dimensional array, a one-dimensional infinite chain and a one-dimensional double-chain supramolecular structure. Bioassay results of the compounds indicated that the dibutyltin complexes 3 and 4 have potent in vitro cytotoxic activity against two human tumor cell lines, CoLo205 and Bcap37, while the diethyltin complexes 1 and 2 display weak cytotoxic activity. Copyright © 2008 John Wiley & Sons, Ltd. [source] Synthesis, characterization and biological activity of diphenyltin(IV) complexes of N -(3,5-dibromosalicylidene)-,-amino acid and their diphenyltin dichloride adductsAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 1 2006Laijin Tian Abstract Diphenyltin(IV) complexes of N -(3,5-dibromosalicylidene)-,-amino acid, Ph2Sn[3,5-Br2 -2-OC6H2 CHNCH(R)COO] (where R = H, Me, i -Pr, Bz), and their 1:1 adducts with diphenyltin dichloride, Ph2Sn[3,5-Br2 -2-OC6H2CHNCH(R)COO]·Ph2SnCl2, have been synthesized and characterized by elemental analysis, IR and NMR (1H, 13C and 119Sn) spectra. The crystal structure of Ph2Sn[3,5-Br2 -2-OC6H2CHNCH(i -Pr)COO] shows a distorted trigonal bipyramidal geometry with the axial locations occupied by a carboxylate,oxygen and a phenolic,oxygen atom of the ligand, and that of Ph2Sn[3,5-Br2 -2-OC6H2CHNCH(i -Pr)COO]·Ph2SnCl2 reveals that the two tin atoms are joined via the carbonyl atom of the ligand to form a mixed organotin binuclear complex. Bioassay indicates that the compounds possess better cytotoxic activity against three human tumor cell lines (HeLa, CoLo205 and MCF-7) than cis -platin and moderate antibacterial activity against two bacteria (E. coli and S. aureus). Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis and In-Vitro Antitumor Activities of Some Mannich Bases of 9-Alkyl-1,2,3,4-tetrahydrocarbazole-1-onesARCHIV DER PHARMAZIE, Issue 3 2009Jing Chen Abstract A novel series of 2-substituted aminomethyl-9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 5a,q was synthesized via aminomethylation of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 4a,e with hydrochlorides of the respective amines 6a,m. The structures of these newly synthesized compounds were characterized by 1H-NMR, MS, and elemental analysis. All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines including human non-small lung cancer cells (A549), human gastric adenocarcinoma (SGC), human colon cancer cell (HCT116), human myeoloid leukemia cells (K562), and one multi-drug resistant subline (KB-VCR). Most compounds showed moderate to potent cytotoxic activity against the tested cell lines. Preliminary mechanism research indicated that the most promising compound, 2-diethylaminomethyl-9-methyl-1,2,3,4-tetrahydrocarbazole-1-one 5c, exhibited a potential inhibitory effect against microtubule. [source] Diorganotin(IV) Derivatives of Substituted Benzohydroxamic Acids with High Antitumor ActivityCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2004Qingshan Li Abstract A series of diorganotin(IV) and dichlorotin(IV) derivatives of 4-X-benzohydroxamic acids, [HL1 (X = Cl) or HL2 (X = OCH3)] formulated as [R2SnL2] (R = Me, Et, nBu, Ph or Cl; L = L1 or L2), along with their corresponding mixed-ligand complexes [R2Sn(L1)(L2)] have been prepared and characterized by FT-IR, 1H, 13C, and 119Sn NMR spectroscopy, mass spectrometry, elemental analysis, and melting points. In addition, single-crystal X-ray diffraction analyses were carried out for [Me2SnL2] (L = L1 or L2), which show coordination structures intermediate between distorted octahedra and bicapped tetrahedra. The hydroxamate ligands are asymmetrically coordinated by the oxygen atoms, the carbonyl oxygen atom is further away from the metal center than the other oxygen atom. The complexes are stable monomeric species; most of them are soluble not only in chlorohydrocarbon solvents, but also in alcohols and hydroalcoholic solutions. In polar solvents, the mixed-ligand complexes gradually decompose into the corresponding single-ligand complex couples. The complexes exhibit in vitro antitumor activities (against a series of human tumor cell lines) which, in some cases, are identical to, or even higher than, that of cisplatin. For the dialkyltin complexes, the activity increases with the length of the carbon chain of the alkyl ligand and is higher in the case of the chloro-substituted benzohydroxamato ligand. The [nBu2Sn(L1)2] complex displays a high in vivo activity against H22 liver and BGC-823 gastric tumors, and has a relatively low toxicity. [source] A Novel Sulfated Holostane Glycoside from Sea Cucumber Holothuria leucospilotaCHEMISTRY & BIODIVERSITY, Issue 7 2010Hua Han Abstract A new sulfated holostane glycoside, leucospilotaside B (1), together with the two related structurally known compounds holothurin B2 (2) and holothurin B (3), was isolated from sea cucumber Holothuria leucospilota collected from the South China Sea. The structure of 1 was elucidated by spectral analysis (1H-, 13C-, and 2D-NMR, ESI-MS, and HR-ESI-MS) and chemical methods. The compounds 1,3 possess the same disaccharide moiety, but were different in the side chains of the triterpene aglycone. Compound 1 showed significant cytotoxicities against four human tumor cell lines, HL-60, MOLT-4, A-549, and BEL-7402. [source] Design, Synthesis, and Biological Evaluation of New Territrem B AnaloguesCHEMISTRY & BIODIVERSITY, Issue 4 2005Xiangrui Jiang Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined. [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] Synthesis, Antiproliferative Evaluation, and Structure,Activity Relationships of 3-ArylquinolinesCHEMMEDCHEM, Issue 10 2008Zhu-Ping Xiao The cytotoxicity of substituted 3-aryl-4-chloroquinolines: A series of 3-arylquinolines were designed, synthesized and evaluated as antitumor agents. While the majority of the 34 compounds evaluated exhibited potent cytotoxicity in one or more of the human tumor cell lines tested, two compounds were identified as potential leads, with high activity against human hepatocellular liver carcinoma (Hep-G2), human erythromyeloblastoid leukemia (K562) and human oral epidermoid carcinoma (KB) cell lines, and lacking significant cytotoxicity against the normal human liver cell line (L02). [source] Impact of the Aliphatic Dicarboxylate Chain of Novel Dinuclear Palladium(II) Complexes: Synthesis and Biological EvaluationCHINESE JOURNAL OF CHEMISTRY, Issue 2 2010Enjun Gao Abstract Five dinuclear palladium(II) complexes with HOOC(CH2)nCOOH (n=2,6) and 2,2,-bipyridine ligands were synthesigned by a reaction with K2PdCl4. To prepare such complexes with different aliphatic dicarboxylate chain lengths was in an attempt to correlate this length factor, which influences the biological activity of the complexes, with fluorescence spectra, DNA cleavage and cytotoxic activity. The results indicate that the complexes bind to fish sperm DNA (FS-DNA) in an intercalative mode via fluorescence spectra, and the five complexes show different cleavage of supercoiled DNA, and then a cytotoxicity assay of these dinuclear palladium(II) complexes on human tumor cell lines was performed. In most of the cell lines, complex 5 (n=6) and 4 (n=5) showed much higher cytotoxicity than cis -platin. On the other hand, complex 3 (n=4) was found to be moderately active, and complex 1 (n=2), complex 2 (n=3) were found only marginally cytotoxic. Implications of these findings were discussed from a structure-activity relationship. [source] | ||||||||||||||||||||||||||||