title: The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics.
abstract: We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b]furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy.
authors.affiliation: Gause Institute of New Antibiotics, 11B. Pirogovskaya Street, Moscow 119021, Russia. shchekotikhin@mail.ru
authors.forename: Andrey E
authors.initials: AE
authors.lastname: Shchekotikhin
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Glazunova
authors.forename: Lyubov G
authors.initials: LG
authors.lastname: Dezhenkova
authors.forename: Elena K
authors.initials: EK
authors.lastname: Shevtsova
authors.forename: Valery F
authors.initials: VF
authors.lastname: Traven'
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
authors.forename: Maria N
authors.initials: MN
authors.lastname: Preobrazhenskaya
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D011758:Pyrroles; D013876:Thiophenes; D004247:DNA; D004264:DNA Topoisomerases, Type I