Synthesis, antitumor cytotoxicity, and DNA-binding of novel N-5,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides.
A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamides with the suitable (omega-aminoalkyl)hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure-activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.
Antonini
I
I
Department of Chemical Sciences, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy. antonini@camserv.unicam.it
Polucci
P
P
Magnano
A
A
Martelli
S
S
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005470:Fluorometry; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000166:Acridines; D000970:Antineoplastic Agents; D004247:DNA