title: Synthesis of aryl-substituted naphthalenoids as potent topoisomerase inhibitors.
abstract: Twelve new aryl-substituted naphthalenoids (1-7, 9, 10, and 13-16) together with four known ones (8, and 11- 13) have been designed and synthesized. Their antitumor activities were evaluated by sulforhodamine B assay on human breast cancer MDA-MB-231, human lung cancer A549 and human cervical cancer HeLa cell lines. Four compounds (2, 4, 10 and 12) showed potent inhibitory activities against the growth of the three cell lines with IC50 between 0.34-3.49 µM, and were more potent than the reference etoposide (IC50 3.67-13.78 µM). DNA relaxation assay revealed that compound 2 showed potent inhibitory activity against Topo IIα in vitro. The structure-activity relationships of these compounds were discussed, suggesting that further structural optimizations of aryl-substituted naphthalenoids could lead to the discovery of potent antitumor agents targeting topoisomerases.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Wang
authors.initials: W
authors.lastname: Chen
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China. yshen@sdu.edu.cn.
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000951:Antigens, Neoplasm; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009281:Naphthalenes; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II