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Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2018 May 01; Vol. 26 (8), pp. 1547-1559. Date of Electronic Publication: 2018 Feb 10. - Publication Year :
- 2018
-
Abstract
- A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF-α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF-α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF-α. Notable anti-angiogenesis activity was observed for 20, 21 and 22.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Angiogenesis Inhibitors chemical synthesis
Angiogenesis Inhibitors chemistry
Animals
Cell Survival drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Lipopolysaccharides antagonists & inhibitors
Lipopolysaccharides pharmacology
Mice
Molecular Structure
Neuroprotective Agents chemical synthesis
Neuroprotective Agents chemistry
Nitrites metabolism
Phthalimides chemical synthesis
Phthalimides chemistry
RAW 264.7 Cells
Structure-Activity Relationship
Tumor Necrosis Factor-alpha metabolism
Angiogenesis Inhibitors pharmacology
Drug Design
Neuroprotective Agents pharmacology
Nitrites antagonists & inhibitors
Phthalimides pharmacology
Tumor Necrosis Factor-alpha antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 26
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29472124
- Full Text :
- https://doi.org/10.1016/j.bmc.2018.01.032