title: Design, synthesis and anticancer activity of oxoaporphine alkaloid derivatives.
abstract: A series of new oxoaporphine derivatives were synthesized and their inhibitory activity of topoisomerase I, cytotoxicity and DNA-binding properties were studied. Oxoaporphine can strongly inhibit topoisomerase I at concentrations of 5-50 µM and the cytotoxicity of the derivatives are more potent than their lead compound. Hypochromism, broadening and red shift in the absorption spectra were observed when these compounds bind to calf thymus DNA (CT DNA). These spectral characteristics were consistent with the intercalative binding of these compounds.
authors: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Guangxi Medical University , Nanning, Guangxi , PR China.
authors: Yong-Biao
authors: YB
authors: Wei
authors: Ying-Xin
authors: YX
authors: Li
authors: Hui
authors: H
authors: Song
authors: Xian-Jin
authors: XJ
authors: Feng
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D001060:Aporphines; D059004:Topoisomerase I Inhibitors; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I
keywords: Cytotoxicity; DNA binding; oxoaporphine alkaloids; synthesis; topoisomerase I inhibitor