Studies on the Enantiomers of RC-33 as Neuroprotective Agents: Isolation, Configurational Assignment, and Preliminary Biological Profile. Issue 11 (7th September 2013)

• Record Type: Journal Article
• Authors: Rossi, Daniela; Pedrali, Alice; Marra, Annamaria; Pignataro, Luca; Schepmann, Dirk; Wünsch, Bernhard; Ye, Lian; Leuner, Kristina; Peviani, Marco; Curti, Daniela; Azzolina, Ornella; Collina, Simona
• Is Part Of: Chirality. Volume 25:Issue 11(2013:Nov.)
• Page Start: 814
• Page End: 822
• Publication Date: 2013-09-07
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22223
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>In this study we addressed the role of chirality in the <named-content id="d469e789" content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">biological activity</named-content> of <bold>RC-33</bold>, recently studied by us in its racemic form. An <named-content id="d469e794" content-type="reactionType chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">asymmetric synthesis</named-content> procedure was the first experiment, leading to the desired enantioenriched <bold>RC-33</bold> but with an enantiomeric excess (<italic>ee</italic>) not good enough for supporting the in vitro investigation. An <named-content id="d469e803" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enantioselective</named-content> high‐performance <named-content id="d469e806" content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">liquid chromatography</named-content> (HPLC) procedure was then successfully carried out, yielding both <bold>RC-33</bold> enantiomers in amounts and optical purity suitable for the pharmacological study. The absolute configuration of pure enantiomers was easily assigned exploiting the <named-content id="d469e811" content-type="reactionType chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">asymmetric synthesis</named-content> previously devised. As emerged in the preliminary in vitro biological investigation, (<italic>S</italic>)‐ and <bold>(R)-RC-33</bold> possess a comparable affinity towards the σ<sub>1</sub> receptor and a very a similar behavior in the calcium influx assay, resulting in an equally effective σ<sub>1</sub> 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 <named-content id="d469e826" content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">biological activity</named-content> of <bold>RC-33</bold>. <italic>Chirality 25:814–822, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </abstract>