Role of the azinomycin naphthoate and central amide in sequence-dependent DNA alkylation and cytotoxicity of epoxide-bearing substructures.
Studies report a strong correlation between duplex DNA alkylation and in vitro cytotoxicity for a series of azinomycin partial structures 2-6 bearing the biologically relevant epoxide. Compounds lacking the naphthoate ester (e.g., 5 and 6) were poorly reactive toward DNA and were biologically inactive, as were compounds bearing the naphthoate but lacking the terminal carboxamide (e.g., 2). Compounds were evaluated for cytotoxicity against two breast cancer cell lines. [structure: see text]
D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity*; D053961:Azabicyclo Compounds; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D018736:DNA Adducts / Q000737:chemistry / Q000235:genetics; D004151:Dipeptides; D004852:Epoxy Compounds / Q000737:chemistry* / Q000633:toxicity*; D006020:Glycopeptides; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D053961:Azabicyclo Compounds; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004151:Dipeptides; D004852:Epoxy Compounds; D006020:Glycopeptides; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; C051055:azinomycin B; C051054:azinomycin A; D004247:DNA