Download PDF
Planta Med 2019; 85(06): 496-502
DOI: 10.1055/a-0826-0483
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Alkaloids from Leaves of Pilea aff. martinii

Ai Doan Thi Thuy
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
2   National University of Agriculture, Trau Quy, Hanoi, Vietnam
,
Van Trinh Thi Thanh
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
,
Huong Doan Thi Mai
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
,
Huyen Tram Le
3   Hanoi University of Science and Technology (HUST), Hanoi, Vietnam
,
Marc Litaudon
4   Institut de Chimie des Substances Naturelles, CNRS-ICSN, UPR 2301, Université Paris-Sud, Paris, France
,
Van Hung Nguyen
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
,
Van Minh Chau
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
,
Van Cuong Pham
1   Advanced Center for Bioorganic Chemistry, Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
› Author Affiliations
Further Information

Publication History

received 13 September 2018
revised 05 December 2018

accepted 19 December 2018

Publication Date:
21 February 2019 (online)

    Permissions and Reprints

Abstract

Two new phenanthroquinolizidine alkaloids (1 and 2) and a new piperidine derivative (3) were isolated from the leaves of Pilea aff. martinii together with 3 known alkaloids: julandine (4), cryptopleurine (5), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (6). Their structures were determined by spectral data analyses including mass spectrometry and 2-dimensional nuclear magnetic resonance data. The absolute configurations of 1–3 were established by comparison of their experimental circular dichroism data with the calculated electronic circular dichroism spectra. The isolated compounds were evaluated for their cytotoxicity against 4 cancer cell lines: KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). The new phenanthroquinolizidine pileamartine D (2) showed strong and selective proliferation inhibition toward KB and HepG-2 cells with IC50 values of 25 and 27 nM, respectively. Pileamartine C (1), julandine (4), and cryptopleurine (5) exhibited cytotoxicity against 4 tested cancer cell lines with IC50 values less than 1 µM.

Key words

Pilea aff. martinii - Urticaceae - pileamartine - cytotoxic - alkaloid - pileamartine - phenanthroquinolizidine

Supporting Information

 

  • References

  • 1 Wink M. Quinolizidine alkaloids: biochemistry, metabolism, and function in plants and cell Suspension cultures. Planta Med 1987; 53: 509-514
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Donaldson GR, Atkinson MR, Murray AW. Inhibition of protein synthesis in Ehrlich ascites-tumour cells by the phenanthrene alkaloids tylophorine, tylocrebrine and cryptopleurine. Biochem Biophys Res Commun 1968; 31: 104-109
    CrossrefPubMedGoogle Scholar
  • 3 Staerk D, Lykkeberg AK, Christensen J, Budnik BA, Abe F, Jaroszewski JW. In vitro cytotoxic activity of phenanthroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells. J Nat Prod 2002; 65: 1299-1302
    CrossrefPubMedGoogle Scholar
  • 4 Gao W, Busson S, Grill SP, Gullen EA, Hu YC, Huang X, Zhong S, Kaczmarek C, Gutierrez J, Francis S, Baker DC, Yu S, Cheng YC. Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents. Bioorg Med Chem Lett 2007; 17: 4338-4342
    CrossrefPubMedGoogle Scholar
  • 5 Fu Y, Lee SK, Min HY, Lee T, Lee J, Cheng M, Kim S. Synthesis and structure-activity studies of antofine analogues as potential anticancer agents. Bioorg Med Chem Lett 2007; 17: 97-100
    CrossrefPubMedGoogle Scholar
  • 6 Sherry RC. Phenanthroindolizidines and phenanthroquinolizidines: promising alkaloids for anti-cancer therapy. Curr Bioact Compd 2009; 5: 2-19
    CrossrefPubMedGoogle Scholar
  • 7 Yang CW, Lee YZ, Kang IJ, Barnard DJ, Jan JT, Lin D, Huang CW, Yeh TK, Chao YS, Lee SJ. Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus. Antiviral Res 2010; 88: 160-168
    CrossrefPubMedGoogle Scholar
  • 8 Bhutani KK, Sharma GL, Ali M. Plant based antiamoebic drugs; part I. Antiamoebic activity of phenanthroindolizidine alkaloids; common structural determinants of activity with emetine. Planta Med 1987; 53: 532-536
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Gopalakrishnan C, Shankaranarayan D, Kameswaran L, Natarajan S. Pharmacological investigations of tylophorine, the major alkaloid of Tylophora indica . Ind J Med Res 1979; 69: 513-520
    PubMedGoogle Scholar
  • 10 Gopalakrishnan C, Shankaranarayanan D, Nazimudeen SK, Kameswaran L. Effect of tylophorine, a major alkaloid of Tylophora indica, on immunopathological and inflammatory reactions. Ind J Med Res 1980; 71: 940-948
    PubMedGoogle Scholar
  • 11 Gellert E, Riggs NV. Crytopleurine: and alkaloid of Cryptocarya pleurosperma White & Francis. Aust J Chem 1954; 7: 113-120
    CrossrefPubMedGoogle Scholar
  • 12 Luo Y, Liu Y, Luo D, Gao X, Li B, Zhang G. Cytotoxic alkaloids from Boehmeria siamensis . Planta Med 2003; 69: 842-845
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Cai XF, Jin X, Lee D, Yang YT, Lee K, Hong YS, Lee JH, Lee JJ. Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells. J Nat Prod 2006; 69: 1095-1097
    CrossrefPubMedGoogle Scholar
  • 14 Krmpotic E, Farnsworth NR, Messmer WM. Cryptopleurine, an active antiviral alkaloid from Boehmeria cylindrica (L.) Sw. (Urticaceae). J Pharm Sci 1972; 61: 1508-1509
    CrossrefPubMedGoogle Scholar
  • 15 Al-Shamma A, Drake SD, Guagliardi LE, Mitscher LA, Swayze JK. Antimicrobial alkaloids from Boehmeria cylindrica . Phytochemistry 1982; 21: 485-487
    CrossrefPubMedGoogle Scholar
  • 16 Hart NK, Johns SR, Lamberton JA. Minor alkaloids of Boehmeria platyphylla Don. (family Urticaceae). II. Isolation of cryptopleurine and a new seco-phenanthroquinolizidine alkaloid. Aust J Chem 1968; 21: 2579-2581
    CrossrefPubMedGoogle Scholar
  • 17 Hoffmann JJ, Luzbetak DJ, Torrance SJ, Cole JR. Cryptopleurine, cytotoxic agent from Boehmeria caudata (Urticaceae) and Cryptocarya laevigata (Lauraceae). Phytochemistry 1978; 17: 1448
    CrossrefPubMedGoogle Scholar
  • 18 Doan Thi TA, Trinh Thi TV, Doan Thi Mai H, Le HT, Litaudon M, Chau VM, Pham VC. Pileamartines A and B: alkaloids from Pilea aff. martinii with a new carbon skeleton. Tetrahedron Lett 2018; 59: 1909-1912
    CrossrefPubMedGoogle Scholar
  • 19 Diedrich C, Grimme SJ. Systematic investigation of modern quantum chemical methods to predict electronic circular dichroism spectra. Phys Chem A 2003; 107: 2524-2539
    CrossrefPubMedGoogle Scholar
  • 20 Ding Y, Li XC, Ferreira D. Theoretical calculation of electronic circular dichroism of the rotationally restricted 3, 8′′-biflavonoid morelloflavone. J Org Chem 2007; 72: 9010-9017
    CrossrefPubMedGoogle Scholar
  • 21 Cragg JE, Herbert RB. Synthesis of the alkaloids, 3′,4′-dimethoxy-2-(2-piperidyl)acetophenone, julandine, and cryptopleurine. J Chem Soc Perkin Trans 1 1982; (00) 2487-2490
    PubMedGoogle Scholar
  • 22 Kim S, Lee T, Lee E, Lee J, Fan GJ, Lee SK, Kim D. Asymmetric total syntheses of (−)-antofine and (−)-cryptopleurine using (R)-(E)-4-(tributylstannyl)but-3-en-2-ol. J Org Chem 2004; 69: 3144-3149
    CrossrefPubMedGoogle Scholar
  • 23 Demole E, Demole C. A chemical study of Burley tobacco flavour (Nicotiona tobacum L.) V. Identification and synthesis of the novel terpenoid alkaloids 1, 3, 6, 6-petramethyl-5, 6, 7, 8-tetrahydro-isoquinolin-8-one and 3, 6, 6-trirnethyl-5, 6-dihydro-7H-2-pyrindin-7-one. Helv Chim Acta 1975; 58: 523-531
    CrossrefPubMedGoogle Scholar
  • 24 Spartanʼ14. Irvine, CA, USA: Wavefunction; 2013
    PubMedGoogle Scholar
  • 25 Gaussian 09, Revision B.01. Wallingford, CT, USA: Gaussian; 2010
    Google Scholar
  • 26 Bruhn T, Schaumlöffel A, Hemberger Y, Pecitelli G. SpecDis version 1.71. Berlin, Germany, 2017. Available at: https://specdis-software.jimdo.com Accessed July 20, 2018
    PubMedGoogle Scholar
  • 27 Bruhn T, Schaumlöffel A, Hemberger Y, Bringmann G. SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality 2013; 25: 243-249
    CrossrefPubMedGoogle Scholar
  • 28 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
    CrossrefPubMedGoogle Scholar