New steroid sulfatase inhibitors based on 1,2,4-oxadiazole sulfamate derivatives - Project - Bridge of Knowledge


New steroid sulfatase inhibitors based on 1,2,4-oxadiazole sulfamate derivatives

One of the methods against hormone-dependent breast cancer (HDBC) is hormone therapy. It involves the administration of substances that inhibit the action of the enzymes responsible for biosynthesis of steroids (especially estrogens) that stimulate the development of cancerous tissue. Scientists have identified three enzyme pathways responsible for the biosynthesis of active forms of estrogens: aromatase, 17β-hydroxysteroid dehydrogenase, and steroid sulfatase (STS). For many years, substances such as tamoxifen or anastrozole have been used to treat breast cancer in pre- and postmenopausal women. Unfortunately, because of the many side effects and cases of cancer recurrence, it is necessary to develop new inhibitors. Recent studies have shown that STS activity in cancerous breast cancer tissue is a million times higher than aromatase activity. This means that steroid sulfatase plays a key role in the development of breast cancer, making it an attractive molecular target for more effective fight against HDBC. Over the past few years, intensive research has been ongoing into the discovery of new STS inhibitors. Replacement in the steroid structure of the sulphate moiety with sulfamate resulting in irreversible inhibition of STS activity proved to be crucial. Unfortunately, most substances that exhibited high levels of STS inhibition had undesirable estrogenic properties that led to tumor progression. In order to reduce these properties, work began on compounds that mimic the steroid structure of natural STS substrates in a very good way and at the same time do not show estrogenic properties. As a result, a huge group of compounds was obtained, which includes, among others, derivatives of triazoles, benzophenols, biphenyls and phenylindoles. This project involves the design, synthesis and evaluation of the biological activity of new steroid sulfatase inhibitors. Using molecular modeling techniques, it will be possible to select the most promising compounds, which will reduce the time as well as cost of research. The resulting new STS inhibitors will be subjected to in vitro assay studies. We plan to receive a number of new substances that will be potentially used in HDBC therapy


Financial Program Name:
Narodowe Centrum Nauki (NCN) (National Science Centre)
UMO-2020/37/N/NZ7/02535 z dnia 2021-01-19
Realisation period:
2021-01-19 - 2024-01-18
Project manager:
dr inż. Karol Biernacki
Realised in:
Department of Organic Chemistry
Request type:
National Research Programmes
Domestic project
Verified by:
Gdańsk University of Technology

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