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Clerodane diterpenoids from Casearia kurzii and their cytotoxic activities

  • Yuan Shuo
  • Chenyue Zhang
  • Xueyuan Yang
  • Feng Liu
  • Qi Zhang
  • Annan Li
  • Jun Ma
  • Dongho Lee
  • Yasushi Ohizumi
  • Yuanqiang GuoEmail author
Note
  • 62 Downloads

Abstract

A search for bioactive natural products as anticancer lead compounds resulted in the isolation of one previously undescribed and three known clerodane diterpenoids (14) from Casearia kurzii. The structures of these compounds were established by analysis of their NMR, MS, and electronic circular dichroism data. The cytotoxic activities of four compounds against three human cancer cell lines were evaluated. Compound 2 was found to be the most active with an IC50 value of 4.1 μM against HeLa cells, and was selected to investigate the possible cytotoxic mechanism.

Graphic abstract

Keywords

Casearia kurzii Clerodane diterpenoids Cytotoxic activities Apoptosis Cell cycle 

Notes

Acknowledgements

This work was supported by the National University Student Innovation Program of Nankai University, the National Natural Science Foundation of China (No. U1703107), the Natural Science Foundation of Tianjin, China (No. 16JCYBJC27700), and Hundred Young Academic Leaders Program of Nankai University.

Compliance with ethical standards

Conflict of interest

The authors have declared no competing interests.

Supplementary material

11418_2019_1324_MOESM1_ESM.doc (231 kb)
Appendix A: Supplementary data. 1D and 2D NMR spectra of 1 are available as supplementary data. Supplementary data related to this article can be found online. 1 (DOC 231 kb)

References

  1. 1.
    Editorial Committee of the Flora of China (1999) Flora of China. Science Press, Beijing, pp 69–71Google Scholar
  2. 2.
    Xia L, Guo Q, Tu PF, Chai XY (2015) The genus Casearia: a phytochemical and pharmacological overview. Phytochem Rev 14:99–135CrossRefGoogle Scholar
  3. 3.
    Chen CY, Cheng YB, Chen SY, Chien CT, Kuo YH, Guh JH, Khalil AT, Shen YC (2008) New bioactive clerodane diterpenoids from the roots of Casearia membranacea. Chem Biodivers 5:162–167CrossRefPubMedGoogle Scholar
  4. 4.
    dos Santos AG, Ferreira PM, Vieira Júnior GM, Perez CC, Gomes Tininis A, Silva GH, Bolzani Vda S, Costa-Lotufo LV, Pessoa Cdo O, Cavalheiro AJ (2010) Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumor human cells. Chem Biodivers 7:205–215CrossRefPubMedGoogle Scholar
  5. 5.
    Kanokmedhakul S, Kanokmedhakul K, Buayairaksa M (2007) Cytotoxic clerodane diterpenoids from fruits of Casearia grewiifolia. J Nat Prod 70:1122–1126CrossRefPubMedGoogle Scholar
  6. 6.
    Vieira-Júnior GM, Gonçalves TO, Regasini LO, Ferreira PM, Pessoa CO, Costa Lotufo LV, Torres RB, Boralle N, Bolzani VS, Cavalheiro AJ (2009) Cytotoxic clerodane diterpenoids from Casearia obliqua. J Nat Prod 72:1847–1850CrossRefGoogle Scholar
  7. 7.
    Wang B, Wang XL, Wang SQ, Shen T, Liu YQ, Yuan HQ, Lou HX, Wang XN (2013) Cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia balansae. J Nat Prod 76:1573–1579CrossRefPubMedGoogle Scholar
  8. 8.
    Whitson EL, Thomas CL, Henrich CJ, Sayers TJ, Mcmahon JB, Mckee TC (2010) Clerodane diterpenes from Casearia arguta that act as synergistic TRAIL sensitizers. J Nat Prod 73:2013–2018CrossRefPubMedGoogle Scholar
  9. 9.
    Williams RB, Norris A, Miller JS, Birkinshaw C, Ratovoson F, Andriantsiferana R, Rasamison VE, Kingston DG (2007) Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar. J Nat Prod 70:206–209CrossRefPubMedGoogle Scholar
  10. 10.
    Ma J, Yang X, Zhang Q, Zhang X, Xie C, Tuerhong M, Zhang J, Jin DQ, Lee D, Xu J, Ohizumi Y, Guo Y (2019) Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii. Bioorg Chem 85:558–567CrossRefPubMedGoogle Scholar
  11. 11.
    Xu J, Zhang Q, Wang MC, Ren QH, Sun YH, Jin DQ, Xie CF, Chen HQ, Ohizumi Y, Guo YQ (2014) Bioactive clerodane diterpenoids from the twigs of Casearia balansae. J Nat Prod 77:2182–2189CrossRefPubMedGoogle Scholar
  12. 12.
    Aimaiti S, Suzuki A, Saito Y, Fukuyoshi S, Goto M, Miyake K, Newman DJ, O’Keefe BR, Lee KH, Nakagawa-Goto K (2018) Corymbulosins I–W, cytotoxic clerodane diterpenes from the bark of Laetia corymbulosa. J Org Chem 83:951–963CrossRefPubMedGoogle Scholar
  13. 13.
    Gibbons S, Graya AI, Watermana PG (1996) Clerodane diterpenes from the bark of Casearia tremula. Phytochemistry 41:565–570CrossRefGoogle Scholar
  14. 14.
    Li XC, Ferreira D, Ding Y (2010) Determination of absolute configuration of natural products: theoretical calculation of electronic circular dichroism as a tool. Curr Org Chem 14:1678–1697CrossRefPubMedGoogle Scholar
  15. 15.
    Shen YC, Wang CH, Cheng YB, Wang LT, Guh JH, Chien CT, Khalil AT (2004) New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea. J Nat Prod 67:316–321CrossRefPubMedGoogle Scholar
  16. 16.
    Gao S, Sun D, Wang G, Zhang J, Jiang Y, Li G, Zhang K, Wang L, Huang J, Chen L (2016) Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells. Bioorg Chem 69:121–128CrossRefPubMedGoogle Scholar
  17. 17.
    Yu JS, Lee D, Lee SR, Lee JW, Choi CI, Jang TS, Kang KS, Kim KH (2018) Chemical characterization of cytotoxic indole acetic acid derivative from mulberry fruit (Morus alba L.) against human cervical cancer. Bioorg Chem 76:28–36CrossRefPubMedGoogle Scholar
  18. 18.
    Yao GD, Sun Q, Song XY, Huang XX, Zhang Y, Song SJ (2018) 1,3-Diphenylpropanes from Daphne giraldii induced apoptosis in hepatocellular carcinoma cells through nuclear factor kappa-B inhibition. Bioorg Chem 77:619–624CrossRefPubMedGoogle Scholar
  19. 19.
    Li DH, Li JY, Xue CM, Han T, Sai CM, Wang KB, Lu JC, Jing YK, Hua HM, Li ZL (2017) Antiproliferative dimeric aporphinoid alkaloids from the roots of Thalictrum cultratum. J Nat Prod 80:2893–2904CrossRefPubMedGoogle Scholar
  20. 20.
    Mirzaei H, Shokrzadeh M, Modanloo M, Ziar A, Riazi GH, Emami S (2017) New indole-based chalconoids as tubulin-targeting antiproliferative agents. Bioorg Chem 75:86–98CrossRefPubMedGoogle Scholar
  21. 21.
    Pertuit D, Larshini M, Brahim MA, Markouk M, Mitaine-Offer AC, Paululat T, Delemasure S, Dutartre P, Lacaille-Dubois MA (2017) Triterpenoid saponins from the roots of Spergularia marginata. Phytochemistry 139:81–87CrossRefPubMedGoogle Scholar
  22. 22.
    King KL, Cidlowski JA (1998) Cell cycle regulation and apoptosis. Annu Rev Physiol 60:601–617CrossRefPubMedGoogle Scholar
  23. 23.
    Liu F, Yang XY, Ma J, Yang YL, Xie C, Tuerhong M, Jin DQ, Xu J, Lee D, Ohizumi Y, Guo YQ (2017) Nitric oxide inhibitory daphnane diterpenoids as potential anti-neuroinflammatory agents for AD from the twigs of Trigonostemon thyrsoideus. Bioorg Chem 75:149–156CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy 2019

Authors and Affiliations

  • Yuan Shuo
    • 1
  • Chenyue Zhang
    • 1
  • Xueyuan Yang
    • 1
  • Feng Liu
    • 1
  • Qi Zhang
    • 1
  • Annan Li
    • 1
  • Jun Ma
    • 1
  • Dongho Lee
    • 2
  • Yasushi Ohizumi
    • 3
  • Yuanqiang Guo
    • 1
    Email author
  1. 1.State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, College of PharmacyNankai UniversityTianjinPeople’s Republic of China
  2. 2.Department of Biosystems and Biotechnology, College of Life Sciences and BiotechnologyKorea UniversitySeoulRepublic of Korea
  3. 3.Kansei Fukushi Research InstituteTohoku Fukushi UniversitySendaiJapan

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