title: Synthesis of a series of cytotoxic 2-acyl-1,2-dihydroellipticines which inhibit topoisomerase II.
abstract: An array of novel 2-acyl-1,2-dihydroellipticines was prepared and evaluated for in vitro cytotoxicity in a variety of human cancer cell lines. The ellipticine analogs were also tested for inhibition of topoisomerase II in both decatenation and cleavable complex formation assays. Some of the new ellipticine derivatives were prepared by acylation of ellipticine with acid chlorides in tetrahydrofuran, followed by reduction of the intermediate 2-acylellipticinium ions with sodium cyanoborohydride. Others were synthesized by acylation of ellipticine with p-nitrophenyl chloroformate, reduction of the 2-acylellipticinium ion with sodium cyanoborohydride, and displacement of the p-nitrophenoxide anion with a variety of oxygen and nitrogen nucleophiles. The cytotoxicities of the new 2-acyl-1,2-dihydroellipticines varied widely, and correlated well with their topoisomerase II inhibitory activities.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Purdue University, West Lafayette IN 47907, USA.
authors.forename: R
authors.initials: R
authors.lastname: Devraj
authors.forename: J
authors.initials: J
authors.lastname: Jurayj
authors.forename: J A
authors.initials: JA
authors.lastname: Fernandez
authors.forename: J F
authors.initials: JF
authors.lastname: Barrett
authors.forename: M
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004611:Ellipticines; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors