RT Journal Article
SR Electronic
T1 Structure-Activity Relationships for Thiolytic Cleavage Rates of Antitumor Drugs in the 4'-(9-Acridinylamino) methanesulfonanilide Series
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1027
OP 1035
VO 12
IS 6
A1 BRUCE F. CAIN
A1 WILLIAM ROBERT WILSON
A1 BRUCE C. BAGULEY
YR 1976
UL http://molpharm.aspetjournals.org/content/12/6/1027.abstract
AB 4'-(9-Acridinylamino)methanesulfon-m-anisidide (NSC 156303; m-AMSA) is an experimental broad-spectrum antitumor agent also displaying immunosuppressive and antiviral activity. In pharmacological studies this compound had a short half-life in vivo as a result of rapid chemical reaction with proteins. Interaction of m-AMSA with thiols and other nucleophiles has been studied and the reaction products characterized. The reaction of greatest biological relevance is nucleophilic attack at the acridine C-9 position by thiols. The relationships among structure, thiolysis rates, and antileukemic activity of over 50 substituted acridines have been investigated. Rapid reaction with thiols is not a prerequisite for antileukemic (L1210) activity with these agents.