Oxiranylmethyloxy or thiiranylmethyloxy-azaxanthones and -acridone analogues as potential topoisomerase I inhibitors.
A total of seven new oxyranylmethyloxy or thiiranylmethyloxy group substituted 5-azaxanthones and -acridones analogues were synthesized and tested for their biological activities for cancer cell lines and topoisomerases. Among the compounds, compound 5, 3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone, showed effective topoisomerase I inhibitory activity, 50% and 27% inhibition ratio at 100 and 20muM, respectively. This result is the first finding of the function of 5-azaxanthone compounds for topoisomerase I inhibition and can provide a novel skeleton for the anticancer drug development process.
Cho
Hee-Ju
HJ
College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk 712-702, Republic of Korea.
Jung
Mi-Ja
MJ
Kwon
Youngjoo
Y
Na
Younghwa
Y
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000166:Acridines; D000970:Antineoplastic Agents; D001372:Aza Compounds; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D044004:Xanthones