title: Synthesis of 1-/2-substituted-[1,2,3]triazolo[4,5-g]phthalazine-4,9-diones and evaluation of their cytotoxicity and topoisomerase II inhibition.
abstract: Studies on antitumor heterocyclic quinones containing nitrogens revealed that the number and position of nitrogens on the heterocyclic ring have significance on cytotoxicity of quinones. In our continuous effort to find more cytotoxic quinone compounds, we designed triazolophthalazine analogues in order to introduce more nitrogens on the heterocyclic quinones. 1-/2-Substituted-[1,2,3]triazolo[4,5-g]phthalazine-4,9-diones were synthesized by 1,3-dipolar addition of phthalazine-5,8-dione and 4-methoxybenzyl azide by modification of previously reported method. The cytotoxicity of the synthesized compounds was evaluated by a SRB (sulforhodamine B) assay against nine types of human cancer cell lines and inhibition against topoisomerase II (Topo II) of them was assessed by a decatenation assay. Most of the synthesized compounds showed considerably higher cytotoxicity than that of doxorubicin. Also, topoisomerase II inhibitory activity of the tested compounds was higher than that of etoposide and IC(50) values of the compounds were 19.4-64.5 microM.
authors.affiliation: School of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Jin Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Rhee
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Chong-Ock
authors.initials: CO
authors.lastname: Lee
authors.forename: Hea-Young
authors.initials: HY
authors.lastname: Park Choo
mesh_terms: D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012235:Rhodamines; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D001391:Azo Compounds; D016227:Benzoquinones; D010793:Phthalazines; D012235:Rhodamines; D059005:Topoisomerase II Inhibitors; C022027:lissamine rhodamine B; C004532:quinone; C043388:phthalazine; D004250:DNA Topoisomerases, Type II