title: Solid phase synthesis and biological activity of tuftsin conjugates.
abstract: New tuftsin/retro-tuftsin conjugates were designed and synthesized using a classical fluorenylmethoxycarbonyl (Fmoc) solid phase procedure. All the peptide conjugates were divided into three series: 1,4-dihydroxyanthraquinone (type A), 1-nitroacridine (type B), and 4-carboxyacridone (type C) derivatives. In type A conjugates, the N-terminal group of the peptide chain is directly connected to the anthraquinone ring at C1 (Scheme 1), whereas types B and C conjugates possess an amide bond formed between the carboxyl group of heterocyclic molecule and the N-termini of the tuftsin chain. The in vitro cytotoxic activity of the tuftsin conjugates and their precursors using two human tumor cell lines (lung adenocarcinoma (A549) and myeloblastic leukemia (HL-60)) was investigated. The analogues from groups A and C exhibited low cytotoxic activity, whereas several compounds of type B showed a potent and selective cytotoxic activity against tested tumor cell lines. None of the examined tuftsin conjugates demonstrated any significant effect on the catalytic activity of types I and II DNA topoisomerases.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-233 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kukowska-Kaszuba
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dzierzbicka
authors.forename: Marcin
authors.initials: M
authors.lastname: Serocki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Skladanowski
mesh_terms: D000166:Acridines / Q000737:chemistry; D054831:Acridones; D000595:Amino Acid Sequence; D000880:Anthraquinones / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055162:Biocatalysis; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014405:Tuftsin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000166:Acridines; D054831:Acridones; D000880:Anthraquinones; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C041300:acridone; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; D014405:Tuftsin