Počet záznamů: 1

Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?

  1. 1.
    0458613 - UOCHB-X 2017 RIV US eng J - Článek v odborném periodiku
    Kasal, Alexander - Buděšínský, Miloš - Mareš, Pavel - Krištofíková, Z. - Leitao, A. J. - Sá e Melo, M. L. - Silva, M. M. C.
    Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?.
    Steroids. Roč. 105, Jan (2016), s. 12-18 ISSN 0039-128X
    Grant CEP: GA ČR(CZ) GA305/09/0846; GA ČR(CZ) GBP304/12/G069
    Institucionální podpora: RVO:61388963 ; RVO:67985823
    Klíčová slova: neurosteroids * NMR spectrometry * GABA(A) receptor * TBPS-test
    Kód oboru RIV: CC - Organická chemie; FH - Neurologie, neurochirurgie, neurovědy (FGU-C)
    Impakt faktor: 2.282, rok: 2016

    Seven steroid epoxides were prepared from 5 alpha-pregn-2-en-20-one and 5 alpha-pregn-3-en-20-one and their side-chain derivatives. All compounds were tested in vitro for binding to gamma-aminobutyric acid (GABA(A)) receptor, some of them also in vivo for anticonvulsant action. 2 alpha,3 alpha-Epoxy-5 alpha-pregnan-20-one inhibited the TBPS binding to the GABA(A) receptor and showed a moderate anticonvulsant action in immature rats. In contrast, its 3 alpha,4 alpha-isomer was inactive. More polar epoxide derivatives, modified at the side chain were less active or inactive. Noteworthy, diol 20, the product of trans-diaxial opening of the 2 alpha,3 alpha-epoxide 4, was not able to inhibit the TBPS binding, showing that the activity of the epoxide is due to the compound itself and not to its hydrolytic product. The 3 alpha-hydroxyl group is known to be essential for the GABA(A) receptor binding. Despite the shortness of in vivo effects which are probably due to metabolic inactivation of the products prepared, our results show that the 2 alpha,3 alpha-epoxy ring is another structural pattern with ability to bind the GABA(A)R.
    Trvalý link: http://hdl.handle.net/11104/0258860