Antisulfatase, Osteogenic, and Anticancer Activities of Steroid Sulfatase Inhibitor EO-33 in Mice.
J Med Chem
; 62(11): 5512-5521, 2019 06 13.
Article
em En
| MEDLINE
| ID: mdl-31062594
ABSTRACT
Steroid sulfatase (STS) is a key enzyme involved in the biosynthesis of estrogens from inactive sulfated steroids. After we reported EO-33 as a potent in vitro STS inhibitor without undesirable estrogenic activity and with osteogenic properties, we are now interested in validating EO-33's in vivo potential to inhibit STS, to prevent bone deterioration, and to reduce estrogen-dependent tumor growth. A scale-up synthesis was first elaborated to prepare the multigram quantity of EO-33 needed to perform in vivo studies. EO-33 blocked the uterine weight stimulated by estrone sulfate in ovariectomized mice by 69% and the STS activity in the liver by 81%. It also produced a selective estrogen receptor modulator effect as assessed by measuring the tibia weight and calcium content. Using a human breast cancer (MCF-7 xenograft) model in nude mice, EO-33 blocked 90% of tumor growth induced by estradiol sulfate, and no toxic effect was observed by assessing the body and liver weights.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Ácidos Sulfônicos
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Esteril-Sulfatase
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Inibidores Enzimáticos
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article