Substituted 2,5'-Bi-1H-benzimidazoles: topoisomerase I inhibition and cytotoxicity.
Several 2'-aryl-5-substituted-2,5'bi-1H-benzimidazole derivatives were synthesized and evaluated as topoisomerase I poisons and for their cytotoxicity toward the human lymphoblast cell line RPMI 8402. This study focused on 18 2,5'-bi-1H-benzimidazole derivatives which contained either a 5-cyano, a 5-(aminocarbonyl), or a 5-(4-methylpiperazinyl) group. Among these bibenzimidazoles, the pharmacological activity of 2'-phenyl derivatives and the influence of the different positional isomers of either a 2'-tolyl group or a 2'-naphthyl moiety on cytotoxicity and topoisomerase I inhibitory activity were determined.
Kim
J S
JS
Department of Pharmaceutical Chemistry, Rutgers, State University of New Jersey, Piscataway, 08855, USA.
Gatto
B
B
Yu
C
C
Liu
A
A
Liu
L F
LF
LaVoie
E J
EJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors