ellipticines

Summary

Summary: Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.

Top Publications

  1. Garbett N, Graves D. Extending nature's leads: the anticancer agent ellipticine. Curr Med Chem Anticancer Agents. 2004;4:149-72 pubmed
    ..Considerable research efforts have been directed towards gaining a greater understanding of the mechanism of action of these drugs that will aid further in the optimization of drug design. ..
  2. Stiborova M, Rupertova M, Schmeiser H, Frei E. Molecular mechanisms of antineoplastic action of an anticancer drug ellipticine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006;150:13-23 pubmed
    ..The study forms the basis to further predict the susceptibility of human cancers to ellipticine. ..
  3. de Melo L, Braga S, Barone P. Pattern recognition methods investigation of ellipticines structure-activity relationships. J Mol Graph Model. 2007;25:912-20 pubmed
    ..These descriptors have been only recently discussed in the literature as new possible universal parameters for defining the biological activity of several classes of compounds. ..
  4. Stiborova M, Bieler C, Wiessler M, Frei E. The anticancer agent ellipticine on activation by cytochrome P450 forms covalent DNA adducts. Biochem Pharmacol. 2001;62:1675-84 pubmed
    ..The DNA adduct formation we describe is a novel mechanism for the ellipticine action and might in part explain its tumor specificity. ..
  5. Deane F, O Sullivan E, Maguire A, Gilbert J, Sakoff J, McCluskey A, et al. Synthesis and evaluation of novel ellipticines as potential anti-cancer agents. Org Biomol Chem. 2013;11:1334-44 pubmed publisher
    ..04-5.2 ?M). 6-Methylellipticine was the most potent growth inhibitory compound assessed (GI(50) = 0.47-0.9 ?M). N-Alkylation of 6-methylellipticine was found to reduce this response with GI(50) values in the range of 1.3-28 ?M. ..
  6. Andrews W, Panova T, Normand C, Gadal O, Tikhonova I, Panov K. Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription. J Biol Chem. 2013;288:4567-82 pubmed publisher
    ..Here we report that a number of the ellipticines, including 9-hydroxyellipticine, are potent and specific inhibitors of Pol-I transcription, with IC(50) in ..
  7. Kizek R, Adam V, Hrabeta J, Eckschlager T, Smutný S, Burda J, et al. Anthracyclines and ellipticines as DNA-damaging anticancer drugs: recent advances. Pharmacol Ther. 2012;133:26-39 pubmed publisher
    Over the past forty years, anthracyclines and ellipticines have attracted attention as promising cytostatics. In this review, we focus on their mechanisms of cytoxicity, DNA-damaging effects and adverse side-effects...
  8. Kuo P, Hsu Y, Chang C, Lin C. The mechanism of ellipticine-induced apoptosis and cell cycle arrest in human breast MCF-7 cancer cells. Cancer Lett. 2005;223:293-301 pubmed
  9. Fung S, Yang H, Chen P. Sequence effect of self-assembling peptides on the complexation and in vitro delivery of the hydrophobic anticancer drug ellipticine. PLoS ONE. 2008;3:e1956 pubmed publisher
    ..This work provides essential information for peptide sequence design in the development of self-assembling peptide-based delivery of hydrophobic anticancer drugs. ..

More Information

Publications61

  1. Liu J, Xiao Y, Allen C. Polymer-drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine. J Pharm Sci. 2004;93:132-43 pubmed
    ..Overall, a good correlation was obtained between drug formulation characteristics and findings from our polymer-drug compatibility studies. Further optimization of the PEO-b-PCL micelle formulation for Ellipticine was also performed. ..
  2. Peng Y, Li C, Chen L, Sebti S, Chen J. Rescue of mutant p53 transcription function by ellipticine. Oncogene. 2003;22:4478-87 pubmed
    ..These results demonstrate that ellipticine can restore transcription function to mutant p53. This property may contribute to the selectivity of ellipticine-derived compounds against tumor cell lines expressing mutant p53. ..
  3. Harding M, Grummitt A. 9-hydroxyellipticine and derivatives as chemotherapy agents. Mini Rev Med Chem. 2003;3:67-76 pubmed
    ..quinone-imine intermediates, phosphorylation of p53 suppressor proteins and cytotoxicity relative to the parent ellipticines. Recent studies have focused on the mechanism of inhibition of phosphorylation of the mutant type of p53 ..
  4. Stiborova M, Bořek Dohalská L, Aimová D, Kotrbova V, Kukacková K, Janouchová K, et al. Oxidation pattern of the anticancer drug ellipticine by hepatic microsomes - similarity between human and rat systems. Gen Physiol Biophys. 2006;25:245-61 pubmed
    ..The results underline the suitability of rat species as a model to evaluate human susceptibility to ellipticine. ..
  5. Huang Y, Blower P, Yang C, Barbacioru C, Dai Z, Zhang Y, et al. Correlating gene expression with chemical scaffolds of cytotoxic agents: ellipticines as substrates and inhibitors of MDR1. Pharmacogenomics J. 2005;5:112-25 pubmed
    ..To determine MDR1 interactions of five ellipticines with diverse MDR1-r values, we employed MDR1-transport and cytotoxicity assays, using MDR1 inhibitors and siRNA-..
  6. Canals A, Purciolas M, Aymami J, Coll M. The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs. Acta Crystallogr D Biol Crystallogr. 2005;61:1009-12 pubmed
    ..The 1.5 A resolution structure of ellipticine complexed to a 6 bp oligonucleotide unveils its mode of binding and enables a detailed analysis of the distorting effects of the drug on the DNA. ..
  7. Kuo Y, Kuo P, Hsu Y, Cho C, Lin C. Ellipticine induces apoptosis through p53-dependent pathway in human hepatocellular carcinoma HepG2 cells. Life Sci. 2006;78:2550-7 pubmed
    ..Taken together, ellipticine decreased the cell growth and induced apoptosis in HepG2 cell. ..
  8. Fung S, Duhamel J, Chen P. Solvent effect on the photophysical properties of the anticancer agent ellipticine. J Phys Chem A. 2006;110:11446-54 pubmed
    ..A relatively large red shift of emission in liposomes indicated that ellipticine may be in a more polar environment with respect to the lipid bilayer, possibly close to the hydrophilic interface. ..
  9. Vehar B, Hrast M, Kovac A, Konc J, Mariner K, Chopra I, et al. Ellipticines and 9-acridinylamines as inhibitors of D-alanine:D-alanine ligase. Bioorg Med Chem. 2011;19:5137-46 pubmed publisher
    ..New members of both families were obtained through similarity search and synthesis. Ellipticines and 9-acridinylamines were both found to possess inhibitory activity against Ddl from Escherichia coli and ..
  10. Zhang L, Bennett W, Zheng T, Ouyang P, Ouyang X, Qiu X, et al. Effect of Cholesterol on Cellular Uptake of Cancer Drugs Pirarubicin and Ellipticine. J Phys Chem B. 2016;120:3148-56 pubmed publisher
    ..Our results suggest that the traditional understanding of drug permeation and the influence of cholesterol on the small molecule transport is naïve and needs to be re-examined. ..
  11. Kubar T, Jurecka P, Cerny J, Rezac J, Otyepka M, Valdes H, et al. Density-functional, density-functional tight-binding, and wave function calculations on biomolecular systems. J Phys Chem A. 2007;111:5642-7 pubmed
    ..The very favorable time demands of these approaches are discussed, and for each of them, a suitable area of use is proposed on the basis of the results of our analysis. ..
  12. Shahabuddin M, Nambiar M, Moorthy B, Naik P, Choudhary B, Advirao G, et al. A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells. Invest New Drugs. 2011;29:523-33 pubmed publisher
    ..Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis. ..
  13. Gavvala K, Sengupta A, Koninti R, Hazra P. Prototropical and photophysical properties of ellipticine inside the nanocavities of molecular containers. J Phys Chem B. 2013;117:14099-107 pubmed publisher
    ..Deep insight into the molecular picture of these host-guest interactions has been provided by the docking studies followed by quantum chemical calculations. ..
  14. Liu J, Zeng F, Allen C. Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent. J Control Release. 2005;103:481-97 pubmed
    ..These studies demonstrate that although there are no significant interactions between micelle and protein, the properties of the micelle as a delivery vehicle may be strongly influenced by protein-drug interactions. ..
  15. O Reilly E, Kreuzer K. A unique type II topoisomerase mutant that is hypersensitive to a broad range of cleavage-inducing antitumor agents. Biochemistry. 2002;41:7989-97 pubmed
    ..We believe that this mutant defines a new category of type II topoisomerase mutants, namely, those that are hypersensitive to all inhibitors that stabilize the cleavage complex. ..
  16. Verbrugge L, Giesy J, Verbrugge D, Woodin B, Stegeman J. Catalytic and immunochemical properties of hepatic cytochrome P450 1A in three avian species treated with beta-naphthoflavone or isosafrole. Comp Biochem Physiol C Toxicol Pharmacol. 2001;130:67-83 pubmed
    ..Variations in responses among avian species indicate that CYP1A proteins and substrate specificities should be characterized for each species used in PHAH biomonitoring programs. ..
  17. Martinkova E, Dontenwill M, Frei E, Stiborova M. Cytotoxicity of and DNA adduct formation by ellipticine in human U87MG glioblastoma cancer cells. Neuro Endocrinol Lett. 2009;30 Suppl 1:60-6 pubmed
    ..The results found in this study are the first report showing cytotoxicity and DNA adduct formation by ellipticine in glioblastomas. ..
  18. Pamarthy D, Tan M, Wu M, Chen J, Yang D, Wang S, et al. p27 degradation by an ellipticinium series of compound via ubiquitin-proteasome pathway. Cancer Biol Ther. 2007;6:360-6 pubmed
    ..The finding could provide a new tool to further understand the mechanism of p27 degradation. ..
  19. Kriaâ W, Sghaier Hammami B, Masmoudi Allouche F, Benjemaa Masmoudi R, Drira N. The date palm (Phoenix dactylifera L.) micropropagation using completely mature female flowers. C R Biol. 2012;335:194-204 pubmed publisher
  20. Mathe G, Morette C, Hallard M, Blanquet D. Combinations of three or four HIV virostatics applied in short sequences which differ from each other by drug rotation. Preliminary results of the viral loads and CD4 numbers. Biomed Pharmacother. 1997;51:417-26 pubmed
    ..This CD4 restoration limitation can be due to persisting virus, as indicated in some patients by small peaks which may appear on some VL plateaus, though they disappear without treatment change. ..
  21. Samadi Baboli M, Favre G, Canal P, Soula G. Low density lipoprotein for cytotoxic drug targeting: improved activity of elliptinium derivative against B16 melanoma in mice. Br J Cancer. 1993;68:319-26 pubmed
    ..These data suggest that LDL improves the potency of lipophilic cytotoxic drugs against tumours that express LDL receptor activity. ..
  22. Shiizaki K, Ohsako S, Koyama T, Nagata R, Yonemoto J, Tohyama C. Lack of CYP1A1 expression is involved in unresponsiveness of the human hepatoma cell line SK-HEP-1 to dioxin. Toxicol Lett. 2005;160:22-33 pubmed
    ..Our findings demonstrated the presence of endogenous ligands in SK-HEP-1 cells due to the absence of the metabolizing enzyme CYP1A1, but not CYP1B1, which allowed the constitutive expression of AhR target genes. ..
  23. Poljakova J, Forsterova K, Sulc M, Frei E, Stiborova M. Oxidation of an antitumor drug ellipticine by peroxidases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005;149:449-53 pubmed
    ..The implication of the oxidation of ellipticine by peroxidases in its mechanism of action is discussed. ..
  24. Gros L, Delaporte C, Frey S, Decesse J, de Saint Vincent B, Cavarec L, et al. Identification of new drug sensitivity genes using genetic suppressor elements: protein arginine N-methyltransferase mediates cell sensitivity to DNA-damaging agents. Cancer Res. 2003;63:164-71 pubmed
    ..Our data indicate that down-regulation of these enzymes in the GSE-expressing cells would alter one or several steps downstream of the drug-target interaction in the drug-response pathway. ..
  25. Jamison J, Krabill K, Flowers D, Tsai C. In vitro antiviral activity of poly (A-U) and ellipticines. Biochimie. 1990;72:235-43 pubmed
    ..These observations suggest that modulation of a nuclear process may be responsible for the enhanced antiviral activity. ..
  26. Tang H, Jin X, Wang S, Yang D, Cao Y, Chen J, et al. A small molecule compound inhibits AKT pathway in ovarian cancer cell lines. Gynecol Oncol. 2006;100:308-17 pubmed
    ..These data suggest that API-59-OME may be a potent agent to target constitutively activated AKT pathway in ovarian cancer cells. ..
  27. Nayak M, Yang J, Hait W. Effect of a single nucleotide polymorphism in the murine double minute 2 promoter (SNP309) on the sensitivity to topoisomerase II-targeting drugs. Cancer Res. 2007;67:5831-9 pubmed
    ..Given the frequency of SNP309 in the general population (40% in heterozygous T/G and 12% in homozygous G/G condition), our observation may have important implications for the individualization of cancer chemotherapy. ..
  28. Salim A, Garson M, Craik D. New indole alkaloids from the roots of Ochrosia acuminata. J Nat Prod. 2004;67:1719-21 pubmed
    ..9-Methoxyellipticine (3) and ellipticine (4) were responsible for the antitumor activities of the extract. The structures of all compounds were elucidated using MS and NMR methods. ..
  29. Shin C, Snapka R. Patterns of strongly protein-associated simian virus 40 DNA replication intermediates resulting from exposures to specific topoisomerase poisons. Biochemistry. 1990;29:10934-9 pubmed
    ..The protein associated with form I DNA may represent a drug-stabilized "topological complex" between type II topoisomerase and SV40 DNA. ..
  30. Stiborova M, Poljakova J, Martinkova E, Ulrichova J, Simanek V, Dvorak Z, et al. Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5. Toxicology. 2012;302:233-41 pubmed publisher
    ..7 ?M. In liver CYP3A4 is the predominant ellipticine activating CYP species, which is expected to result in efficient metabolism after oral ingestion of ellipticine in humans. ..
  31. Sugikawa E, Tsunoda S, Nakanishi N, Ohashi M. 9-Hydroxyellipticine alters the conformation and DNA binding characteristics of mutated p53 protein. Anticancer Res. 2001;21:2671-5 pubmed
    ..These results suggest that 9HE affects the tertiary structure of mutated p53, which results in the restoration of DNA binding characteristics. ..
  32. Saxena D, Yiu G, Ni X, Huang K, Mantovani R, Jacquemin Sablon A, et al. Characterization of promoter elements involved in the down-regulation of topoisomerase IIalpha expression in a drug-resistant cell line. Gene. 2004;342:145-55 pubmed
    ..Furthermore, gel mobility shift assays showed that the resistant line has a differential binding to the novel TATA-like element, which may be responsible for the down-regulation of topoisomerase IIalpha gene. ..
  33. Bennasar M, Roca T, Ferrando F. Regioselective intramolecular reactions of 2-indolylacyl radicals with pyridines: a direct synthetic entry to ellipticine quinones. J Org Chem. 2005;70:9077-80 pubmed
    ..For substrates bearing a (3-pyridyl)methyl moiety connected to the 3-position of the indole ring, the cyclization provides easy access to ellipticine quinones. ..
  34. Pichard Garcia L, Weaver R, Eckett N, Scarfe G, Fabre J, Lucas C, et al. The olivacine derivative s 16020 (9-hydroxy-5,6-dimethyl-N-[2-(dimethylamino)ethyl)-6H-pyrido(4,3-B)-carbazole-1-carboxamide) induces CYP1A and its own metabolism in human hepatocytes in primary culture. Drug Metab Dispos. 2004;32:80-8 pubmed
  35. Goren A, Topcu G, Bilsel G, Bilsel M, Aydogmus Z, Pezzuto J. The chemical constituents and biological activity of essential oil of Lavandula stoechas ssp. stoechas. Z Naturforsch C. 2002;57:797-800 pubmed
    ..The main components of L. stoechas ssp. stoechas oil were pulegone (40.4%), menthol (18.1%), menthone (12.6%). The essential oil of the plant was evaluated for antibacterial and a panel cytotoxic activities. ..
  36. Moody D, Dyba M, Kosakowska Cholody T, Tarasova N, Michejda C. Synthesis and biological activity of 5-aza-ellipticine derivatives. Bioorg Med Chem Lett. 2007;17:2380-4 pubmed
  37. Kotrbova V, Mrazova B, Moserova M, Martinek V, Hodek P, Hudecek J, et al. Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy. Biochem Pharmacol. 2011;82:669-80 pubmed publisher
    ..Our results demonstrate that both the native 3D structure of cytochrome b(5) and the presence of the heme as an electron transfer agent in this protein enable a shift in ellipticine metabolites formed by CYP1A1/2. ..
  38. Skalickova S, Nejdl L, Kudr J, Ruttkay Nedecky B, Jimenez A, Kopel P, et al. Fluorescence Characterization of Gold Modified Liposomes with Antisense N-myc DNA Bound to the Magnetisable Particles with Encapsulated Anticancer Drugs (Doxorubicin, Ellipticine and Etoposide). Sensors (Basel). 2016;16:290 pubmed publisher
    ..The study succeeded in demonstrating that liposomes are suitable for the transport of anticancer drugs and the antisense oligonucleotide, which can block the expression of the N-myc gene. ..
  39. Pedersen J, Bowman W, Elsegood M, Fletcher A, Lovell P. Synthesis of ellipticine: a radical cascade protocol to aryl- and heteroaryl-annulated[b]carbazoles. J Org Chem. 2005;70:10615-8 pubmed
    ..The protocol has been exemplified with the high-yielding total synthesis of the anticancer alkaloid ellipticine. ..
  40. Haider N, Sotelo E. 1,5-dimethyl-6H-pyridazino[4,5-b]carbazole, a 3-aza bioisoster of the antitumor alkaloid olivacine. Chem Pharm Bull (Tokyo). 2002;50:1479-83 pubmed
    ..The title compound (14) thus obtained in only four steps represents a new 3-aza analog of the antitumor natural product, olivacine. ..
  41. Brown R, Danford F, Gokhale V, Hurley L, Brooks T. Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma is directly mediated through the promoter G-quadruplex. J Biol Chem. 2011;286:41018-27 pubmed publisher
    ..Most importantly, these data present, as far as we are aware, the most direct evidence of intracellular G4-mediated control of a particular promoter. ..
  42. Moody T, Czerwinski G, Tarasova N, Michejda C. VIP-ellipticine derivatives inhibit the growth of breast cancer cells. Life Sci. 2002;71:1005-14 pubmed
    ..These results indicate that VIP-E derivatives function as breast cancer VPAC(1) receptor agonists which inhibit MCF-7 cellular viability. ..
  43. Saeki K, Obi I, Ogiku N, Shigekawa M, Imagawa T, Matsumoto T. Cardioprotective effects of 9-hydroxyellipticine on ischemia and reperfusion in isolated rat heart. Jpn J Pharmacol. 2002;89:21-8 pubmed
    ..Unlike nifedipine, an L-type Ca2+-channel blocker, 9HE did not suppress the contraction of rat papillary muscles. Thus, 9HE exerts the cardioprotective effects against ischemia /reperfusion injury without changing hemodynamic indices. ..
  44. Tran N, Pham X, Tuteja R, Tuteja N. Inhibition of unwinding and ATPase activities of pea MCM6 DNA helicase by actinomycin and nogalamycin. Plant Signal Behav. 2011;6:327-9 pubmed
    ..This study could be useful in our better understanding of the mechanism of plant nuclear DNA helicase unwinding. ..
  45. Xu G, Mawji I, Macrae C, Koch C, Datti A, Wrana J, et al. A high-content chemical screen identifies ellipticine as a modulator of p53 nuclear localization. Apoptosis. 2008;13:413-22 pubmed publisher
    ..Thus, a chemical biology approach has identified a molecule that shifts the localization of p53 and enhances its nuclear activity. ..
  46. Ricci C, Netz P. Docking studies on DNA-ligand interactions: building and application of a protocol to identify the binding mode. J Chem Inf Model. 2009;49:1925-35 pubmed publisher
    ..We propose that this approach can be used to investigate other ligands whose binding mode to DNA remains unknown, yielding a suitable starting point for further theoretical studies such as molecular dynamics simulations. ..
  47. Thompson D, Miller C, McCarthy F. Computer simulations reveal a novel nucleotide-type binding orientation for ellipticine-based anticancer c-kit kinase inhibitors. Biochemistry. 2008;47:10333-44 pubmed publisher
  48. Tylińska B, Jasztold Howorko R, Mastalarz H, Szczaurska Nowak K, Materek P, Wietrzyk J. Synthesis of new 1-phenyl-6H-pyrido[4,3-b]carbazole derivatives with potential cytostatic activity. Acta Pol Pharm. 2011;68:31-7 pubmed
    ..One particular compound 6f exhibited over 20 times better activity against L1210 tumor cell line than the reference ellipticine. ..
  49. Tylińska B, Jasztold Howorko R, Mastalarz H, Kłopotowska D, Filip B, Wietrzyk J. Synthesis and structure-activity relationship analysis of new olivacine derivatives. Acta Pol Pharm. 2010;67:495-502 pubmed
    ..Eight of tested derivatives exhibited significant biological activities, which only weakly depended on side chain length and position of the substituent...
  50. Stiborova M, Rupertova M, Frei E. Cytochrome P450- and peroxidase-mediated oxidation of anticancer alkaloid ellipticine dictates its anti-tumor efficiency. Biochim Biophys Acta. 2011;1814:175-85 pubmed publisher
    ..It also suggests ellipticine reactive metabolites 13-hydroxyellipticine and 12-hydroxyellipticine to be good candidates for targeting to tumors absent from the CYP and peroxidase activation enzymes. ..
  51. Aragon P, Yapi A, Pinguet F, Chezal J, Teulade J, Blache Y. Synthesis and biological evaluation of indoloquinolines and pyridocarbazoles: a new example of unexpected photoreduction accompanying photocyclization. Chem Pharm Bull (Tokyo). 2007;55:1349-55 pubmed
    ..All compounds were less effective than doxorubicin in sensitive cells but their activity wasn't decreased by MDR resistance. ..
  52. Beijer K, Abrahamson A, Brunström B, Brandt I. CYP1A inhibition in fish gill filaments: a novel assay applied on pharmaceuticals and other chemicals. Aquat Toxicol. 2010;96:145-50 pubmed publisher
    ..It is concluded that the modified gill filament EROD assay is useful to screen for waterborne pollutants that inhibit catalytic CYP1A activity in fish gills. ..