Synthesis and evaluation of terbenzimidazoles as topoisomerase I inhibitors.
The synthesis and pharmacological activity of a series of terbenzimidazoles are described. The ability of these derivatives to induce DNA cleavage in the presence of topoisomerase I was evaluated in vitro. These analogs were also assayed for their cytotoxicity in RPMI 8402 cells and the camptothecin-resistant CPT-K5 cells. In addition the potential for these compounds to serve as substrates for MDR1 was also determined. Several terbenzimidazoles exhibited similar cytotoxicity against variants of human tumor cells that either overexpress MDR1 or are camptothecin-resistant.
Sun
Q
Q
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
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004341:Drug Evaluation; D006801:Humans; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D059004:Topoisomerase I Inhibitors