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Steroidal oxathiazine inhibitors of estrone sulfatase

Richard H Peters1, Wan Ru Chao, Barbara Sato

  • 1SRI International, Life Science Division, 333 Ravenswood Avenue Bldg., 100-2, Menlo Park, CA 94025, USA. richard.peters@sri.com

Steroids
|December 12, 2002
PubMed

Insights

New steroidal oxathiazines effectively inhibit estrone sulfatase (an enzyme crucial in estrogen synthesis) and show promise in treating estrogen-receptor-positive breast cancer by reducing tumor growth.

Area of Science:

  • Biochemistry
  • Oncology
  • Medicinal Chemistry

Background:

  • Estrone sulfatase (ES) plays a key role in local estrogen synthesis within breast tumors.
  • Elevated estrone sulfate levels contribute significantly to estrogen production in ER(+) breast cancer.
  • Inhibiting ES is a potential therapeutic strategy for postmenopausal ER(+) breast cancer.

Purpose of the Study:

  • To design and synthesize novel steroidal 2',3'-oxathiazines as estrone sulfatase inhibitors (ESIs).
  • To evaluate the in vitro and in vivo efficacy of these ESIs against breast cancer.
  • To assess the potential of these compounds with reduced estrogenic side effects.

Main Methods:

  • Synthesis of steroidal 2',3'-oxathiazine compounds.
  • In vitro assays using MCF-7 human breast cancer cells to assess ES inhibition and cell growth inhibition.
  • In vivo studies using MCF-7 breast cancer xenografts in Balb/c athymic nude mice.

Main Results:

  • The synthesized oxathiazine compounds demonstrated significant in vitro inhibition of estrone sulfatase in MCF-7 cells.
  • These ESIs effectively inhibited estrone sulfate-induced growth of MCF-7 cells.
  • In vivo experiments showed moderate antitumor activity of the ESIs against breast cancer xenografts.

Conclusions:

  • Novel steroidal oxathiazines are potent inhibitors of estrone sulfatase.
  • These compounds exhibit therapeutic potential for estrogen-dependent breast cancer.
  • The developed ESIs offer a promising approach with potentially reduced side effects.

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