Pantzou, AthanasiaVergou, VarvaraCharalampopoulos, IoannisAvlonitis, NicolaosAlexi, XanthippiMinas, VassiliosΑλέξης, Μιχαήλ Ν.Gravanis, AchilleΚαλογεροπούλου, ΘεοδώραLazaridis, IakovosKatsanou, Efrosini S.Ζερβού, ΜαρίαWASHINGTONDHEA 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.Adobe PDF6569-6587https://hdl.handle.net/10442/122300022-262310.1021/jm900468pengAmerican Chemical Society© AMER CHEMICAL SOC© AMER CHEMICAL SOCJournal of Medicinal ChemistryChemistry, MedicinalNovel Dehydroepiandrosterone Derivatives with Antiapoptotic, Neuroprotective ActivityΆρθρο σε επιστημονικό περιοδικό2009-11-12Δημοσίευση σε περιοδικόPublication in journalΧημείαChemical sciencesFrascati 42Φαρμακευτική χημείαMedicinal chemistryisi - Chemistry, Medicinal includes resources emphasizing the isolation and study of substances with therapeutic potential. Topics of interest are quantitative structure-function relationships, structural characterization and organic syntheses of naturally occurring compounds, and chemical and analytical techniques used in rational drug design. See also the PHARMACOLOGY & PHARMACY category.Φαρμακολογία και ΦαρμακευτικήPharmacology and Pharmacyisi - Pharmacology & Pharmacy covers resources on the discovery and testing of bioactive substances, including animal research, clinical experience, delivery systems, and dispensing of drugs. This category also includes resources on the biochemistry, metabolism, and toxic or adverse effects of drugs.Επιστημονικό άρθροScientific articleΕθνικό Ίδρυμα Ερευνών (ΕΙΕ)Greek Aggregator OpenArchives.gr | National Documentation Centre (EKT)