| Title | Synthetic spiro-neurosteroid analogs exerting structure-specific neuroprotective effects | ||
| Authors | I. Charalampopoulos1, V. Minas1, N. Avlonitis2, T. Calogeropoulou2 and A. Gravanis1
1. Departments of Pharmacology, School of Medicine, University of Crete, Heraklion 2. Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Athens, Greece |
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| Citation | Charalampopoulos, I., Minas, V., Avlonitis, N., Calogeropoulou, T., Gravanis, A.: Synthetic spiro-neurosteroid analogs exerting structure-specific neuroprotective effects, Epitheorese Klin. Farmakol. Farmakokinet. 22(2): 119-121 (2008) | ||
| Publication Date | 23-25 May 2008 | ||
| Full Text Language | English | ||
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| Keywords | Neurosteroids, neuroprotection, Bcl-2, apoptosis. | ||
| Other Terms | Review article | ||
| Summary | To investígate the structure-activity relationships of dehydroepiandrosterone (DHEA) and allopregnanolone (ALLO) as pro-survival factors, their anti-apoptotic effect was compared to that of a long list of structurally related compounds. Their prosurvival actions were found to be structure-specific, confined mainly to conformation 3β-OH-Δ5 for androstenes and 3α-OH for pregnanes. Indeed, 3-keto, Δ4, or C7 hydroxylated androstenes and 3β pregnanes were ineffective. One of the synthetic analogs tested (TC50) was highly effective in protecting sympathoadrenal cells against apoptosis with an EC50: 0,087 nM, compared to DHEA (1 nM). TC50 binds with high affinity to recently described membrane DHEA binding sites (KD at picomolar concentration), and mimics DHEA in inducing prosurvival anti-apoptotic Bcl-2 proteins. Our results suggest that TC50 might prove a lead molecule for the synthesis of novel neuroprotective compounds. | ||
| References | 1. Charalampopoulos I., Tsatsanis C., Dermitzaki E., Alexaki I., Castanas E., Margioris A.N., Gravanis A.: Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal cells against apoptosis, via Bcl-2 antiapoptotic proteins. Proc. Natl. Acad. Sci. USA 1O1: 8209-8214 (2004)
2. Charalampopoulos I., Dermitzaki E., Vardouli L., Tsatsanis C., Stournaras C., Margioris A., Gravanis A.: Dehydroepiandrosterone and allopregnanolone directly stimulate catecholamine production via induction of tyrosine hydroxylase and secretion by affecting actin polymerization. Endocrinology 146: 3309-3318 (2005) 3. Charalampopoulos I., Alexaki V.I., Lazaridis I., Dermitzaki E., Avlonitis N., Tsatsanis C., Calogeropoulou T., Margioris A.N., Castanas E., Gravanis A.: G protein-associated, specific membrane binding sites mediate the neuroprotective effect of dehydroepiandrosterone. FASEB J. 20: 577-9 (2006) |
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| Relative Papers | |||
Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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