Elsevier

Tetrahedron

Volume 56, Issue 20, 12 May 2000, Pages 3133-3138
Tetrahedron

Novel Bioactive Steroidal Alkaloids from Pachysandra procumbens

https://doi.org/10.1016/S0040-4020(00)00232-5Get rights and content

Abstract

(+)-(20S)-20-(Dimethylamino)-3α-(methylbenzoylamino)-11-methylene-5α-pregnane (1), a steroidal alkaloid with a new substitution pattern, was isolated from the entire plant of Pachysandra procumbens, together with four other new steroidal alkaloids, (+)-(20S)-3-(benzoylamino)-20-(dimethylamino)-5α-pregn-2-en-4β-ol (2), (+)-(20S)-20-(dimethylamino)-16α-hydroxy-3β-(3′α-isopropyl)-lactam-5α-pregn-4-one (3), (+)-(20S)-20-(dimethylamino)-3α-(methylbenzoylamino)-5α-pregn-12β-yl acetate (4), and (+)-(20S)-20-(dimethylamino)-3α-(methylsenecioylamino)-5α-pregn-12β-ol (5), as well as two known compounds, (+)-pachysamine H (6) and (+)-pachysandrine B (7). The structures of the new compounds were determined by spectroscopic methods. Compounds 17 were evaluated for their potential cancer chemopreventive properties using an in vitro estrone sulfatase assay.

Introduction

Cancer chemoprevention involves the prevention, delay, or reversal of cancer by the ingestion of dietary or pharmaceutical agents.1., 2., 3. As part of our current work in this area, the entire plant of Pachysandra procumbens Michx. (Buxaceae) was chosen for detailed investigation, since its petroleum ether- and ethyl acetate-soluble extracts showed significant activity in an antiestrogen-binding site assay, as measured by inhibition of 3H-tamoxifen binding.4 We earlier reported the first phytochemical and biological investigation on this plant, with the isolation of several new and known steroidal alkaloids as antiestrogen-binding site inhibitors being described.4 Continued investigation of this species has resulted in the isolation of five additional new compounds, 15, and two known compounds (6 and 7). The structural determination of 15 and the biological evaluation of 17 are reported herein.

One approach worth considering for the treatment of breast cancer involves inhibition of the enzyme estrone sulfatase.5 This enzyme hydrolyzes estrone sulfate forming estrone, and estrone sulfate thereby serves as a reservoir for the generation of estrogens. As demonstrated with clinical breast tumor specimens,6 relative to aromatase, another enzyme that controls estrogen levels, sulfatase levels may be 106-fold greater. Sulfatase can also be amplified in human mammary carcinoma cell lines.7 Hence, sulfatase inhibitors have considerable therapeutic potential for the treatment or control of estrogen-dependent breast cancers. Accordingly, isolates 17 were evaluated for their antiestrogenic properties in an estrone sulfatase inhibition assay.8

Section snippets

Results and Discussion

A molecular formula of C32H48N2O was determined from the HREIMS of compound 1. Comparison of its IR, 1H NMR, and 13C NMR data (Table 1, Table 2) with values for pachysamine H (6)14 and several other recently isolated analogs from plants in the family Buxaceae indicated that 1 was a steroidal alkaloid.10., 11., 12., 13. The presence of a methylbenzoyl moiety in 1 [δC 172.7 (CO), δC 137.0 (C-1′), δC 128.4 (C-2′ and C-6′), 126.5 (C-3′ and C-5′), and 129.0 (C-4′)] was consistent with literature

General procedures

Mps: uncorr.; UV: MeOH; IR: film; 1H and 13C NMR, 1H–13C HMBC and HMQC spectra were recorded on a Bruker Avance DPX-300 and DRX-500 MHz spectrometers with TMS as internal standard; low- and high-resolution mass spectra were obtained on a Finnigan MAT-90 instrument.

Plant material

P. procumbens was obtained as seedlings from Greenwood Propagation, Hebron, IL, in April 1997, and plants were grown to maturity in a greenhouse. A voucher specimen (number PC-0398) has been deposited at the University of Illinois

Acknowledgements

We are grateful to Dr D. D. Soejarto and Mr R. Dvorak, College of Pharmacy, University of Illinois at Chicago, for taxonomic assistance and for the mass spectral data, respectively. Also, we thank Mr S. Totura, University of Illinois Pharmacognosy Field Station, Downers Grove, IL, for the plant cultivation, and Dr R. M. Moriarty, Department of Chemistry, University of Illinois at Chicago, for information on synthetic 11-methylene steroids. This work was supported by program project P01 CA48112,

References (18)

  • M.H. Chiu et al.

    Phytochemistry

    (1992)
  • Atta-ur-Rahman et al.

    Phytochemistry

    (1997)
  • L.W. Wattenberg

    Cancer Res.

    (1985)
  • M.B. Sporn

    Lancet

    (1993)
  • J.M. Pezzuto
  • L.C. Chang et al.

    J. Nat. Prod.

    (1998)
  • M.J. Reed et al.

    Drugs Future

    (1994)
  • R.J. Santen et al.

    Ann. N. Y. Acad. Sci.

    (1986)
  • J.R. Pasqualini et al.

    Breast Cancer Res. Treat.

    (1986)
There are more references available in the full text version of this article.

Cited by (0)

View full text