title: A new series of the SMTP plasminogen modulators with a phenylamine-based side chain.
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.
authors.affiliation: Department of Applied Biological Science, Tokyo Noko University, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Koide
authors.forename: Keiko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Nishimura
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Narasaki
authors.forename: Keiji
authors.initials: K
authors.lastname: Hasumi
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D010960:Plasminogen Activators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013191:Stachybotrys / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D001578:Benzopyrans; D016166:Free Radical Scavengers; D011760:Pyrrolidinones; D010960:Plasminogen Activators