Synthesis and biological evaluation of novel naphthoquinone fused cyclic aminoalkylphosphonates and aminoalkylphosphonic monoester.
A series of novel naphthoquinone fused cyclic alpha-aminophosphonates, 2-alkoxy-3,4-dihydro-2H-naphtho[2,3-e][1,4,2]oxazaphosphinane-5,10-dione 2-oxide 3-17 and naphthoquinone fused cyclic alpha-aminophosphonic monoester 18 were synthesized for the first time. These cyclic alpha-aminophosphonates were evaluated for antitumor activity on four human tumor cell lines, and three of them showed significant cytotoxicity (IC(50): 0.019-5.15 microM) comparable to that of the reference drug doxorubicin. Furthermore, inhibition assays for topoisomerase II-mediated relaxation of supercoiled DNA indicated that the naphthoquinone fused cyclic aminophosphonates were catalytic inhibitors of topoisomerase II.
Wang
B
B
College of Pharmaceutical Sciences, Nankai University, Tianjin, China. binwang@mail.nankai.edu.cn
Miao
Z W
ZW
Wang
J
J
Chen
R Y
RY
Zhang
X D
XD
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000737:chemistry*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004952:Esters; D009285:Naphthoquinones; D063065:Organophosphonates; D004250:DNA Topoisomerases, Type II