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Planta Med 2009; 75(10): 1152-1156
DOI: 10.1055/s-0029-1185483
Natural Product Chemistry
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Phenanthroindolizidine Alkaloids from the Roots of Ficus septica

Amooru G. Damu1 , Ping-Chung Kuo2 , Li-Shian Shi2 , Chia-Ying Li1 , Chung-Ren Su1 , Tian-Shung Wu1
  • 1Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
  • 2Department of Biotechnology, National Formosa University, Yunlin, Taiwan
Further Information

Publication History

received April 17, 2008 revised February 3, 2009

accepted February 17, 2009

Publication Date:
18 March 2009 (online)

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Abstract

Activity-monitored fractionation of the CHCl3 solubles of the MeOH extract of the roots of Ficus septica using cytotoxicity assay led to the isolation of twenty phenanthroindolizidine alkaloids, including ten new ficuseptines E–N (1–10) and ten known compounds. The cytotoxic effects of some of the isolates were tested on gastric adenocarcinoma (NUGC) and nasopharyngeal carcinoma (HONE-1) cell lines and the results demonstrated that, with the exception of dehydrotylophorine, all the tested compounds displayed pronounced cytotoxic activity with significant cell growth inhibitory effects. In addition, 13aR-antofine was found to be highly effective with ED50 values of < 0.1 µg/mL against L-1210, P-388, A-549 and HCT-8 cell lines in another assay.

Key words

Ficus septica - Moraceae - phenanthroindolizidines - cytotoxicity - ficuseptine

References

  • 1 Ratnagiriswaran A N, Venkatachalam K. The chemical examination of Tylophora asthmatica and isolation of the alkaloids tylophorine and tylophorinine.  Indian J Med Res. 1935;  22 433-441
    PubMedGoogle Scholar
  • 2 Li Z, Jin Z, Huang R. Isolation, total synthesis and biological activity of phenanthroindolizidine and phenanthroquinolizidine alkaloids.  Synthesis. 2001;  2365-2378
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Fu Y, Lee S K, Min H Y, Lee T, Lee J, Cheng M, Kima S. Synthesis and structure–activity studies of antofine analogues as potential anticancer agents.  Bioorg Med Chem Lett. 2007;  17 97-100
    CrossrefPubMedGoogle Scholar
  • 4 Suffness M, Douros J. Anticancer agents based on natural product models. Cassady JM, Douros JD Medicinal chemistry, Vol. 16. London; Academic Press 1980: 465-487
    Google Scholar
  • 5 Capo M, Saa J M. (−)-Antofine: a phenanthroindolizidine from Vincetoxicum nigrum.  J Nat Prod. 1989;  52 389-390
    CrossrefPubMedGoogle Scholar
  • 6 Damu A G, Kuo P C, Shi L S, Li C Y, Kuoh C S, Wu P L, Wu T S. Phenanthroindolizidine alkaloids from the stems of Ficus septica.  J Nat Prod. 2005;  68 1071-1075
    CrossrefPubMedGoogle Scholar
  • 7 Liao J C. Moraceae in flora of Taiwan, 2nd edition, Vol. 2. Taipei; Editorial committee of the flora of Taiwan 1996: 177-180
    Google Scholar
  • 8 Holdsworth D, Damas K. Traditional medicinal plants of Morobe province, Papua New Guinea.  Int J Crude Drug Res. 1986;  24 217-225
    PubMedGoogle Scholar
  • 9 Gieni R S, Hayglass K T. Comparison of [3H]thymidine incorporation with MTT- and MTS-based bioassays for human and murine IL‐2 and IL‐4 analysis. Tetrazolium assays provide markedly enhanced sensitivity.  J Immunol Methods. 1995;  187 85-93
    CrossrefPubMedGoogle Scholar
  • 10 Malich G, Markovic B, Winder C. The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines.  Toxicology. 1997;  124 179-192
    CrossrefPubMedGoogle Scholar
  • 11 Wang X, Bastow K F, Sun C M, Lin Y L, Yu H J, Don M J, Wu T S, Nakamura S, Lee K H. Antitumor agents 239. Isolation, structure elucidation, total synthesis, and anti-breast cancer activity of neo-tanshinlactone from Salvia miltiorrhiza.  J Med Chem. 2004;  47 5816-5819
    CrossrefPubMedGoogle Scholar
  • 12 Abe F, Uwase Y, Yamauchi T, Honda K, Hayashi N. Phenanthroindolizidine alkaloids from Tylophora tanakae.  Phytochemistry. 1995;  39 695-699
    CrossrefPubMedGoogle Scholar
  • 13 Russel J H. Alkaloids of Ficus species. Occurrence of indolizidine alkaloids in Ficus septica.  Naturwissenschaften. 1963;  50 443-444
    PubMedGoogle Scholar
  • 14 Baumgartner B, Erdelmeier C AJ, Wright A D, Rali T, Sticher O. An antimicrobial alkaloid from Ficus septica.  Phytochemistry. 1990;  29 3327-3330
    CrossrefPubMedGoogle Scholar
  • 15 Wu P L, Rao K V, Su C H, Kuoh C S, Wu T S. Phenanthroindolizidine alkaloids and their cytotoxicity from the leaves of Ficus septica.  Heterocycles. 2002;  57 2401-2408
    CrossrefPubMedGoogle Scholar
  • 16 Govindachari T R, Viswanathan N, Radhakrishnan J, Charubala R, Nityananda R N, Pai B R. Quaternary alkaloids from Tylophora asthmatica.  Indian J Chem Sect B. 1973;  11 1215-1216
    PubMedGoogle Scholar
  • 17 Abe F, Hirokawa M, Yamauchi T, Honda K, Hayashi N, Ishii M, Imagawa S, Iwahana M. Further investigation of phenanthroindolizidine alkaloids from Tylophora tanakae.  Chem Pharm Bull. 1998;  46 767-769
    CrossrefPubMedGoogle Scholar
  • 18 Cui L, Abliz Z, Xia M, Zhao L, Gao S, He W, Xiang Y, Liang F, Yu S S. On-line identification of phenanthroindolizidine alkaloids in a crude extract from Tylophora atrofolliculata by liquid chromatography combined with tandem mass spectrometry.  Rapid Commun Mass Spectrom. 2004;  18 184-190
    CrossrefPubMedGoogle Scholar
  • 19 Xiang Y, Abliz Z, Li L J, Huang X S, Yu S S. Study of structural characteristic features of phenanthroindolizidine alkaloids by fast atom bombardment with tandem mass spectrometry.  Rapid Commun Mass Spectrom. 2002;  16 1668-1674
    CrossrefPubMedGoogle Scholar
  • 20 Bhutani K K, Ali M, Atal C K. Alkaloids from Tylophora hirsuta.  Phytochemistry. 1984;  23 1765-1769
    CrossrefPubMedGoogle Scholar
  • 21 Mi J F, Fang S D, Chen Y, Xu Y M, Zhang R. The application of circular dichroism on the structure analysis of natural products – diterpenoid dilactones and tylophorines.  Acta Pharm Sin. 1992;  27 197-203
    PubMedGoogle Scholar
  • 22 Li X, Peng J, Onda M, Konda Y, Iguchi M, Harigaya Y. Alkaloids from Cynanchum hancockianum (Asclepiadaceae).  Heterocycles. 1989;  29 1797-1808
    CrossrefPubMedGoogle Scholar
  • 23 Lavault M, Richomme P, Bruneton J. New phenanthroindolizidine N-oxides alkaloids isolated from Vincetoxicum hirudinaria Medic.  Pharm Acta Helv. 1994;  68 225-227
    CrossrefPubMedGoogle Scholar
  • 24 Stærk D, Christensen J, Lemmich E, Duus J Ø, Olsen C E, Jaroszewski J W. Cytotoxicity activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum.  J Nat Prod. 2000;  63 1584-1586
    CrossrefPubMedGoogle Scholar
  • 25 Buckley F T, Rapoport H. Amino acids as chiral educts for asymmetric products. Chirally specific syntheses of tylophorine and cryptopleurine.  J Org Chem. 1983;  48 4222-4232
    CrossrefPubMedGoogle Scholar
  • 26 Komatsu H, Watanabe M, Ohyama M, Enya T, Koyama K, Kanazawa T, Kawahara N, Sugimura T, Wakabayashi K. Phenanthroindolizidine alkaloids as cytotoxic substances in a danaid butterfly, Ideopsis similis, against human cancer cells.  J Med Chem. 2001;  44 1833-1836
    CrossrefPubMedGoogle Scholar
  • 27 Huang X, Gao S, Fan L, Yu S, Liang X. Cytotoxic alkaloids from the roots of Tylophora atrofolliculata.  Planta Med. 2004;  70 441-445
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Gupta R S, Krepinsky J J, Siminovitch I. Structural determinants responsible for the biological activity of (−)-emetine, (−)-cryptopleurine, and (−)-tylocrebrine: structure-activity relationship among related compounds.  Mol Pharmacol. 1980;  18 136-143
    PubMedGoogle Scholar

Prof. Tian-Shung Wu

Department of Chemistry
National Cheng Kung University

1Ta-Shiueh Rd.

Tainan 701

Taiwan

R. O. C.

Phone: + 88 6 62 74 75 38

Fax: + 88 6 62 74 05 52

Email: tswu@mail.ncku.edu.tw

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