Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model.
A new class of pyridobenzophenoxazine compounds has been developed as topoisomerase II inhibitors for anticancer chemotherapy. These compounds were designed based on a proposed model of a quinobenzoxazine self-assembly complex on DNA. They showed excellent inhibitory effects on several tumor cell lines with nanomolar IC50 values. Their cytotoxic potency correlates with their ability to unwind DNA and inhibit topoisomerase II.
Drug Dynamics Institute and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712-1074, USA.
Q
Q
Zeng
Y
Y
Kwok
S M
SM
Kerwin
G
G
Mangold
L H
LH
Hurley
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004278:DNA, Superhelical / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D010078:Oxazines; D059005:Topoisomerase II Inhibitors