Structure Based Design, Synthesis, and Evaluation of Potential Inhibitors of Steroid Sulfatase

• Type: Another Publication in an International Scientific Journal
• Date: 2014

Authors

Costa, EV (Author) Other; Sousa, E (Author) FFUP; Choosang, K (Author) Other; Singh, S (Author) Other; Rocha, J (Author) Other; Lima, RT (Author) Other; Pakkong, P (Author) Other; Ahmed, S (Author) Other; Vasconcelos, MH (Author) FFUP; Montanari, CA (Author) Other; Pinto, MM (Author) FFUP

Journal

Title: Current Topics in Medicinal Chemistry

Vol. 14

Pages: 1033-1044

ISSN: 1568-0266

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 8 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-009-B3W

DOI: 10.2174/1568026614666140324124807

Abstract (EN): The activity of the enzyme steroid sulfatase (STS) is high in breast tumors and elevated levels of STS mRNA expression have been associated with a poor prognosis. Potent STS irreversible inhibitors have been developed, paving the way to use this new type of therapy for the treatment of breast cancer. Several small molecules belonging to a natural products-inspired library of previously obtained inhibitors of tumor cell growth and new molecules planned to be reversible inhibitors of this enzyme were docked into STS. Some of the synthesized xanthone derivatives, which revealed high scores against STS, namely oxo-9H-xanthene-3,6-diyl bis(3-chlorobenzoate) (5), 9-oxo-9H-xanthene-3,6-diyl bis(4-tertbutylbenzoate) (6) and 9-oxo-9H-xanthene-3,6-diyl bis(4-methoxybenzoate) (7) showed poor water solubility. Therefore, formulations of these derivatives with cyclodextrins were prepared and characterized. The compounds were evaluated regarding their effect on the in vitro growth of various human tumor cell lines, as well as the effect in STS inhibition, for the compounds with the most favorable Delta G values. Additionally, the capacity of these derivatives and of some prenyl and acetoxy-benzophenone and xanthones to inhibit the in vitro growth of MCF-7 ER(+) and/or to inhibit STS in a micromolar range was also assessed. Some compounds developed in the present work were shown to be potential STS inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12