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Studies on the Enantiomers of RC-33 as Neuroprotective Agents: Isolation, Configurational Assignment, and Preliminary Biological Profile
Author(s) -
Rossi Daniela,
Pedrali Alice,
Marra Annamaria,
Pignataro Luca,
Schepmann Dirk,
Wünsch Bernhard,
Ye Lian,
Leuner Kristina,
Peviani Marco,
Curti Daniela,
Azzolina Ornella,
Collina Simona
Publication year - 2013
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22223
Subject(s) - chemistry , enantiomer , chirality (physics) , stereoselectivity , enantioselective synthesis , biological activity , chiral column chromatography , agonist , enantiomeric excess , stereochemistry , absolute configuration , combinatorial chemistry , in vitro , receptor , organic chemistry , biochemistry , catalysis , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
In this study we addressed the role of chirality in the biological activity of RC-33 , recently studied by us in its racemic form. An asymmetric synthesis procedure was the first experiment, leading to the desired enantioenriched RC-33 but with an enantiomeric excess ( ee ) not good enough for supporting the in vitro investigation. An enantioselective high‐performance liquid chromatography (HPLC) procedure was then successfully carried out, yielding both RC-33 enantiomers in amounts and optical purity suitable for the pharmacological study. The absolute configuration of pure enantiomers was easily assigned exploiting the asymmetric synthesis previously devised. As emerged in the preliminary in vitro biological investigation, ( S )‐ and (R)-RC-33 possess a comparable affinity towards the σ 1 receptor and a very a similar behavior in the calcium influx assay, resulting in an equally effective σ 1 receptor agonist. Overall, the results obtained so far suggest that the interaction with the biological target is nonstereoselective and leads us to hypothesize that there is a lack of stereoselectivity in the biological activity of RC-33 . Chirality 25:814–822, 2013 . © 2013 Wiley Periodicals, Inc.