title: Synthesis of podophyllotoxin congeners as potential DNA topoisomerase II inhibitors.
abstract: We have synthesized a number of new podophyllotoxin congeners in which the A-ring is opened and the C-ring is aromatic. These are based on the chemically modified structures of the naturally occurring podophyllum lignan, diphyllin. These have been synthesized by employing the Michael Initiated Ring Closure methodology. These lignans exhibited considerable DNA topoisomerase II inhibition and were devoid of topoisomerase I inhibition; they did not exhibit very significant activities in the in vitro human tumour cell lines assay. The results obtained provide insights into the structure-activity relationships and the design of chemically modified podophyllotoxin congeners useful in cancer chemotherapy.
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002417:Cattle; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D017705:Lignans / Q000737:chemistry; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013950:Thymus Gland / Q000201:enzymology; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D017705:Lignans; D059005:Topoisomerase II Inhibitors; D011034:Podophyllotoxin