Aporphine Alkaloids and their Reversal Activity of Multidrug Resistance (MDR) from the Stems and Rhizomes of Sinomenium acutum

  • Min, Yong-Deuk (Natural Products Laboratory, College of Pharmacy, Sungkyunkwan University) ;
  • Choi, Sang-Un (Korea Research Institute of Chemical Technology) ;
  • Lee, Kang-Ro (Natural Products Laboratory, College of Pharmacy, Sungkyunkwan University)
  • Published : 2006.08.01

Abstract

Chromatographic separation of the MeOH extract from the stems and rhizomes of Sinomemium acutum led to the isolation of nine alkaloids and a lignan. Their structures were determined to be dauriporphine (1), bianfugecine (2), dauriporphinoline (3), menisporphine (4), (-)-syringaresinol (5), N-feruloyltyramine (6), acutumine (7), dauricumine (8), sinomenine (9), and magnoflorine (10) by spectroscopic means. These compounds were examined for their P-gp mediated MDR reversal activity in human cancer cells. Compound 1 showed the most potent P-gp MDR inhibition activity with an $ED_{50}$ value $0.03\;{\mu}g/mL$ and $0.00010\;{\mu}g/mL$ in the MESSA/DX5 and HCT15 cells, respectively.

Keywords

References

  1. Al-Howiriny, T. A., Zemaitis, M. A., Gao, C., Hadden, C. E., and Martin, G. E., Thalibealine, a novel tetrahydroprotoberberine - aporphine dimeric alkaloid from Thalictrum wangii. J. Nat. Prod., 64, 819-822 (2001) https://doi.org/10.1021/np010095y
  2. Choi, S. U., Kim, N. Y., Choi, E. J., Kim, K. H., and Lee, J. O., Establishment of doxorubicin-resistant subline derived from HCT15 human colorectal cancer cells. Arch. Pharm. Res., 19, 342-347 (1996) https://doi.org/10.1007/BF02976376
  3. Fukuda, N., Yonemitsu, M., and Kimura, T., Studies on the constituents of the stems of Tinospora tuberculata BEUMEE I. N-trans- and N-cis-feruloyl tyramine, and a new phenolic glucoside, tinotuberide. Chem. Pharm. Bull., 31, 156-161 (1983) https://doi.org/10.1248/cpb.31.156
  4. Hou, C-Y. and Xue, H., Studies on the chemical constituents of Menispermum dauricum DC., Acta. Pharm. Sinica., 20, 112- 117 (1985)
  5. Kunitomo, J. and Satoh, M., Structure of menisporphine: a new type of isoquinoline alkaloid. Chem. Pharm. Bull., 30, 2659- 2660 (1982) https://doi.org/10.1248/cpb.30.2659
  6. Kunitomo, J. and Satoh, M., Structure and synthesis of menisporphine, a new type of isoquinoline alkaloid : alkaloids of Menispermum dauricum DC. (9). Tetrahedron, 39, 3261- 3265 (1983) https://doi.org/10.1016/S0040-4020(01)91573-X
  7. Kunitomo, J., Kaede, S., and Satoh, M., The structure of 2,3 - dihydro menisporphine and the synthesis of dauriporphine, oxoisoaporphine alkaloids from Menispermum Dauricum DC.. Chem. Pharm. Bull., 33, 2778-2782 (1985) https://doi.org/10.1248/cpb.33.2778
  8. Marsaioli, A. J., Reis, F. de A. M., Magalhaes, A. F., and Ruveda, E. A., 13C- NMR analysis of aporphine alkaloids. Phytochemistry, 18, 165-169 (1979) https://doi.org/10.1016/S0031-9422(00)90938-5
  9. Otsuka, H., Ito, A., Fujioka, N., Kawamata, I., Kasai, R., Yamasaki, K., and Satoh, T., Butenolides from Sinomenium acutum. Phytochemistry, 33, 389-392 (1993) https://doi.org/10.1016/0031-9422(93)85525-V
  10. Saxena, N. K. and Bhakuni, D. S., The quaternary alkaloids of Cocculus laurifolius DC.. J. of Indian Chem. Soc., LVI, 1020- 1023 (1979)
  11. Shouxun, Z., Wencai, Y., Ninghua, T., Haoru, Z., and Zuncheng X., Anovel oxoisoaporphine alkaloid from the rhizome of Menispermum dauricum. J. China Pharmaceutical University, 20, 312 (1989)
  12. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 82, 1107-1112 (1990) https://doi.org/10.1093/jnci/82.13.1107
  13. Sugimoto, Y., Babiker, H. A. A., Inanaga, S., Kato, M., and Isogai, A., Oxoisoaporphines from Menispermum dauricum. Phytochemistry, 52, 1431-1435 (1999) https://doi.org/10.1016/S0031-9422(99)00330-1
  14. Sugimoto, Y., Babiker, H. A. A., Saisho, T., Furumoto, T., Inanaga, S., and Kato, M., Chloriated alkaloids in Menispermum dauricum DC. root culture. J. Org. Chem., 66, 3299-3302 (2001) https://doi.org/10.1021/jo001494l
  15. Vermes, B., Seligmann, O., and Wagner, H., Synthesis of biologically actibe tetrahydrofurofuranlignan-(syringin, pinoresinol)- mono-and bis-glucosides. Phytochemistry, 30, 3098-3089 (1991)
  16. Wang, Y., Zhou, L., and Li, R., Study progress in Sinomenium acutum (Thunb.) Rehd. et Wils.. Zhong Yao Cai, 25, 209-211 (2002)
  17. Yan X., Zhou, J., and Xie, G., Traditional chinese medicines : molecular structures, natural sources and applications. Ashgate, pp.738 (1999)
  18. Yoshihiro, T., Kazuo, T., Shin, M., and Yoshiro, K., C-13 NMR spectra of morphine alkaloids, codeine, thebaine, and sinomenine, and reated compounds. Tetrahedron Lett., 33, 2853-2856 (1975)