The full text of this item is not currently available in HELIOS
|Title:||Novel Dehydroepiandrosterone Derivatives with Antiapoptotic, Neuroprotective Activity|
Katsanou, Efrosini S.
Alexis, Michael N.
|Type:||Journal Article (Scientific Journal article)|
|Abstract:||DHEA analogues with modifications at positions C3 or 07 were synthesized and evaluated for neuroprotective activity against the neural-crest-derived PC12 cell model of serum deprivation-induced apoptosis. The most potent compounds were the spiro-epoxy derivatives 17 beta-spiro[5-androstene-17, 2'-oxiran]-3 beta-ol (20), (20S)-3 beta,21-dihydroxy-17 beta,20-epoxy-5-pregnene (23), and (20R)-3 beta,21-dihydroxy-17 alpha,20-epoxy-5-pregnene (27) with IG(50) values of 0.19 +/- 0.01, 99.0 +/- 4.6, and 6.4 +/- 0.3 nM, respectively. Analogues 20, 23, and 27, up to the micromolar range of concentrations, were unable to activate estrogen receptor alpha and beta (ER alpha and ER beta) or to interfere with ER-dependent gene expression significantly. In addition, they were unable to stimulate the growth of Ishikawa, MCF-7, and LNCaP cells. Our results suggest that the spiro-epoxyneurosteroid derivatives 20, 23, and 27 may prove to be lead molecules for the synthesis of novel neuroprotective agents.|
|Publisher:||American Chemical Society|
|Journal Title:||Journal of Medicinal Chemistry|
|Subject Category:||Science::Chemistry (General)|
Medicine::Pharmacy and materia medica
|Other Identifiers:||DOI: http://dx.doi.org/10.1021/jm900468p|
|Journal web Location :||http://pubs.acs.org/jmc|
|Rights holder:||© AMER CHEMICAL SOC|
|Appears in Collections:||Institute of Biological Research and Biotechnology (IBRB) (until 2012)|
Institute of Organic and Pharmaceutical Chemistry (IOPC) (until 2012)