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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-2-4
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pubmed:abstractText |
Conservative chemical modifications of the core structure of the lead spipethiane (1) afforded novel potent sigma(1) ligands. sigma(1) affinity and sigma(1/)sigma(2) selectivity proved to be favored by the introduction of polar functions (oxygen atom or carbonyl group) in position 3 or 4 (4-6) or by the elongation of the distance between the two hydrophobic portions of the molecule with the simultaneous presence of a carbonyl group in position 4 (8 and 9). The observed cytostatic effect against the human breast cancer cell line MCF-7/ADR, highly expressing sigma(1) receptors, and not against MCF-7, as well as the enhancement of morphine analgesia highlighted the sigma(1) antagonist profile of this series of compounds. In particular, due to its high sigma(1) affinity (pK(i) = 10.28) and sigma(1)/sigma(2) selectivity ratio (29510), compound 9 might be a novel valuable tool for sigma receptor characterization and a suitable template for the rational design of potential therapeutically useful sigma(1) antagonists.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AmantiniConsueloC,
pubmed-author:Del BelloFabioF,
pubmed-author:GiannellaMarioM,
pubmed-author:MattioliLauraL,
pubmed-author:PalmeryMauraM,
pubmed-author:PerfumiMarinaM,
pubmed-author:PiergentiliAlessandroA,
pubmed-author:PiginiMariaM,
pubmed-author:QuagliaWilmaW,
pubmed-author:SantoniGiorgioG,
pubmed-author:TucciPaoloP,
pubmed-author:ZottiMargheritaM
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1261-9
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pubmed:meshHeading |
pubmed-meshheading:20067271-Analgesics,
pubmed-meshheading:20067271-Animals,
pubmed-meshheading:20067271-Antineoplastic Agents,
pubmed-meshheading:20067271-Apoptosis,
pubmed-meshheading:20067271-Binding, Competitive,
pubmed-meshheading:20067271-Breast Neoplasms,
pubmed-meshheading:20067271-Cell Cycle,
pubmed-meshheading:20067271-Cell Line, Tumor,
pubmed-meshheading:20067271-Cell Membrane,
pubmed-meshheading:20067271-Cell Proliferation,
pubmed-meshheading:20067271-Cerebral Cortex,
pubmed-meshheading:20067271-Drug Screening Assays, Antitumor,
pubmed-meshheading:20067271-Female,
pubmed-meshheading:20067271-Guinea Pigs,
pubmed-meshheading:20067271-Humans,
pubmed-meshheading:20067271-Ileum,
pubmed-meshheading:20067271-Jurkat Cells,
pubmed-meshheading:20067271-Male,
pubmed-meshheading:20067271-Mice,
pubmed-meshheading:20067271-Molecular Structure,
pubmed-meshheading:20067271-Pain Measurement,
pubmed-meshheading:20067271-Piperidines,
pubmed-meshheading:20067271-Radioligand Assay,
pubmed-meshheading:20067271-Rats,
pubmed-meshheading:20067271-Receptors, sigma,
pubmed-meshheading:20067271-Spiro Compounds,
pubmed-meshheading:20067271-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
Novel highly potent and selective sigma 1 receptor antagonists related to spipethiane.
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pubmed:affiliation |
Dipartimento di Scienze Chimiche, Università di Camerino, via S. Agostino 1, 62032 Camerino, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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