Abstract |
SMTPs are a family of small-molecule plasminogen modulators that enhance plasminogen activation. SMTP-7, one of the most potent congeners, is effective in treating thrombotic cerebral infarction. The SMTP molecule consists of a tricyclic γ- lactam moiety, a geranylmethyl group, and an N-linked side chain. The presence of both an aromatic group and a negatively ionizable group in the N-linked side chain is crucial for activity. Investigations of the congeners with a phenylglycine-based side chain suggest that a phenolic hydroxy group affects potency. In this study, we isolate and characterize a series of novel SMTP congeners with a phenylamine-based N-linked side chain. Of the 11 congeners isolated, SMTP-19 (with a 4-phenylcarboxylic acid moiety), SMTP-22 (with a 3-hydroxyphenyl-4- carboxylic acid moiety) and SMTP-25 (with a 2-hydroxyphenyl-3- carboxylic acid moiety) are as potent as SMTP-7 in plasminogen-modulating activity. Their isomers with a carboxylic acid group and/or a phenolic hydroxy group at different positions have <40% of the activity of these congeners. Both SMTP-22 and SMTP-25 have >1.7 times more oxygen radical absorbance capacity as compared with SMTP-7.
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Authors | Haruki Koide, Keiko Hasegawa, Naoko Nishimura, Ritsuko Narasaki, Keiji Hasumi |
Journal | The Journal of antibiotics
(J Antibiot (Tokyo))
Vol. 65
Issue 7
Pg. 361-7
(Jul 2012)
ISSN: 1881-1469 [Electronic] England |
PMID | 22511228
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aniline Compounds
- Benzopyrans
- Free Radical Scavengers
- Pyrrolidinones
- Plasminogen Activators
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Topics |
- Aniline Compounds
(chemistry, isolation & purification, pharmacology)
- Benzopyrans
(chemistry, isolation & purification, pharmacology)
- Free Radical Scavengers
(chemistry, isolation & purification, pharmacology)
- Humans
- Plasminogen Activators
(chemistry, isolation & purification, pharmacology)
- Pyrrolidinones
(chemistry, isolation & purification, pharmacology)
- Stachybotrys
(metabolism)
- Structure-Activity Relationship
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