Synthesis and biological evaluation of thiophosphate tricyclic coumarin derivatives as steroid sulfatase inhibitors

Witold Kozak; Mateusz Daśko; Maciej Masłyk; Bartłomiej Gielniewski; Janusz Rachoń; Sebastian Demkowicz

doi:10.1080/10286020.2015.1054815

Synthesis and biological evaluation of thiophosphate tricyclic coumarin derivatives as steroid sulfatase inhibitors

Abstrakt

Steroid sulfatase (STS) enzyme inhibition is an important approach to the management of hormone-dependent breast cancer. In this paper, we report convenient methods for the synthesis and biological evaluation of thiophosphate tricyclic coumarin analogs exhibiting STS activity. The described methods are based on the straightforward preparation of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-2-one, 3-hydroxy- 7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one, and 3-hydroxy-8,9,10,11-tetrahydro- 7H-cyclohepta[c]chromen-6-one and their further modification by the introduction of various thiophosphate moieties. The inhibition properties of the synthesized compounds were tested toward STS isolated from human placenta. Most of the new STS inhibitors possessed good to moderate activity toward STS. During the course of our investigation, the largest inhibitory effects in the STS enzyme assays were observed for the two compounds 3f and 4r, with IC50 values of 13.3 and 30.3mM, respectively (the IC50 value of 1mM for the 665-COUMATE was used as a reference). The structure–activity relationships of the synthesized coumarin derivatives toward STS enzymes are discussed.

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Autorzy (6)

Witold Kozak
Mateusz Daśko dr inż.
Maciej Masłyk
- The John Paul II Catholic University of Lublin Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences
Bartłomiej Gielniewski
- The John Paul II Catholic University of Lublin Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences
Janusz Rachoń prof. dr hab. inż.
Sebastian Demkowicz dr hab. inż.

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Kategoria:: Publikacja w czasopiśmie
Typ:: artykuł w czasopiśmie wyróżnionym w JCR
Opublikowano w:: JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH nr 17, wydanie 11, strony 1091 - 1096,
ISSN: 1028-6020
Język:: angielski
Rok wydania:: 2015
Opis bibliograficzny:: Kozak W., Daśko M., Masłyk M., Gielniewski B., Rachoń J., Demkowicz S.: Synthesis and biological evaluation of thiophosphate tricyclic coumarin derivatives as steroid sulfatase inhibitors// JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH. -Vol. 17, iss. 11 (2015), s.1091-1096
DOI:: Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1080/10286020.2015.1054815
Weryfikacja:: Politechnika Gdańska