Synthesis, Pharmacological Evaluation, and σ1 Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines
| العنوان: | Synthesis, Pharmacological Evaluation, and σ1 Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines |
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| المؤلفون: | Katharina Korpis, Valentina Dal Col, Patrick J. Bednarski, Stefanie Brune, Dirk Schepmann, Bernhard Wünsch, Frauke Weber, Sabrina Pricl, Erik Laurini |
| المساهمون: | Frauke, Weber, Steffi, Brune, Katharina, Korpi, Patrick J., Bednarski, Laurini, Erik, DAL COL, Valentina, Pricl, Sabrina, Dirk, Schepmann, Bernhard, Wünsch |
| المصدر: | Journal of Medicinal Chemistry. 57:2884-2894 |
| بيانات النشر: | American Chemical Society (ACS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Models, Molecular, Stereochemistry, Guinea Pigs, sigma receptors, computer assisted drug design, Antineoplastic Agents, Apoptosis, Plasma protein binding, Molecular Dynamics Simulation, Piperazines, Structure-Activity Relationship, Neoplasms, Drug Discovery, Tumor Cells, Cultured, Animals, Humans, Receptors, sigma, Structure–activity relationship, Homology modeling, sigma receptor, Receptor, Molecular Structure, Chemistry, Brain, Ligand (biochemistry), Affinities, Cell culture, Molecular Medicine, Chromatography, Thin Layer, Protein Binding |
| الوصف: | Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. σ receptor affinity was recorded using receptor material from both animal and human origin. σ1 affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yl]ethanol (7c) revealed the highest affinity at human σ1 receptors (Ki = 6.8 nM). The potent σ1 receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the σ1 receptor was analyzed in detail using the 3D homology model of the σ1 receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human σ1 receptor. |
| وصف الملف: | STAMPA |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de21ded4a7d95a96339e4c5711ed5b77Test https://doi.org/10.1021/jm401707tTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....de21ded4a7d95a96339e4c5711ed5b77 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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