| Synthesis of pyridine derivatives of L-phenylalanine as antisickling reagents. | |
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MedLine Citation:
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PMID: 6716398 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several bicyclic agents composed of L-phenylalanine coupled to various pyridines were synthesized: 2-, 3-, and 4-(L- phenylalanylamino )pyridine. All three compounds at 3 mM gave positive morphological antisickling effects on homozygous SS cells under reduced O2 tension. Studies on two of these compounds, 2- and 3-(L- phenylalanylamino )pyridine, showed that these agents increase the deoxy-HbS solubility ratio, Cs/ Cs0 , by 14% at 20 mM. Observed changes in the mean corpuscular hemoglobin concentration (MCHC) values of treated cells ranged from 4% at 1.3 mM to 15% at 5.6 mM in compound concentration. Very minor lytic activity was found for treated cells, indicating water uptake is responsible for changes in the MCHC. Further, exposure of sickle cells to a 3 mM concentration of these agents also increased by 6- to 7-fold cellular deformability of a treated erythrocyte population as compared to an untreated one at the same total O2 saturation of 47%. These agents demonstrate the potential of bicyclic compounds composed of a common constituent, L-Phe, in the development toward a viable therapeutic agent. |
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Authors:
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J Altman; M Gorecki; M Wilchek; J R Votano; A Rich |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 27 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1984 May |
Date Detail:
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Created Date: 1984-06-18 Completed Date: 1984-06-18 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 596-600 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anemia, Sickle Cell
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blood Antisickling Agents / chemical synthesis* Erythrocytes / drug effects Hemoglobin, Sickle / metabolism Humans Indicators and Reagents Solubility Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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N01-BH-1-3000/BH/FDA HHS |
| Chemical | |
Reg. No./Substance:
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0/Antisickling Agents; 0/Hemoglobin, Sickle; 0/Indicators and Reagents; 0/deoxyhemoglobin, sickle |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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