2,2-dimethyl-2H-pyran-derived alkaloids I. Practical synthesis of acronycine and benzo[b]acronycine and their biological properties.
The 2,2-dimethyl-2H-pyran-derived alkaloids acronycine and its demethylated congeners were prepared in three steps from anthranilic acid and phloroglucinol. The phenylboronic acid-mediated interamolecular cyclization reaction of 1,3-dihydroxyacridone and 3-methylbut-2-enal was employed as a key step, which was also applied to the synthesis of related cytotoxic benzo[b]acronycine. Inhibitory activities of the compounds prepared on topoisomerase I and II as well as their cytotoxicities were evaluated. Cytotoxicity of 2 is closely related to the strong inhibitory activity against topo II at 20 microM level.
Motiur Rahman
A F M
AF
College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Korea.
Liang
Jing Lu
JL
Lee
Seung Ho
SH
Son
Jong Keun
JK
Jung
Mi-Ja
MJ
Kwon
Youngjoo
Y
Jahng
Yurngdong
Y
D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C504489:benzo(b)acronycine; D005047:Etoposide; D004247:DNA; D000175:Acronine; D002166:Camptothecin