title: Synthesis, physicochemical characterization and preliminary pharmacological in vitro evaluation of two novel cytotoxic benzophenone-linked 3,3-dimethyltriazenes.
abstract: The synthesis, physicochemical characterization and preliminary pharmacological evaluation of the cytotoxic effects of two novel substances, 1-(4-benzoylphenyl)-3,3-dimethyltriazene and 1-(2-benzoylphenyl)-3,3-dimethyltriazene is presented. The cytotoxicity of the novel benzophenone-linked triazenes and of ten other 1-phenyl-3,3-dimethyl triazene derivatives as well as of the referent alkylating drug melphalan was assessed using the MTT-dye reduction assay. A panel of human tumor cell lines was used: the chronic lymphoid leukemia SKW-3, the acute promyelocyte leukemia HL-60 and its multi-drug-resistant subline HL-60/Dox. Both novel compounds showed strong cytotoxic activity, comparable to that of the referent alkylating agent melphalan, whereas the ten ring-substituted 1-phenyl-3,3-dimethyl triazenes proved to be far less active in vitro. DNA-fragmentation analysis indicated that after 24 h treatment the novel benzophenone-linked triazenes induced programmed cell death in HL-60 cells.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Medical University-Sofia, Bulgaria. imanolov@mbox.pharmfac.acad.bg
authors.forename: I
authors.initials: I
authors.lastname: Manolov
authors.forename: H J
authors.initials: HJ
authors.lastname: Machulla
authors.forename: G
authors.initials: G
authors.lastname: Momekov
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018922:HL-60 Cells; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles; D014226:Triazenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D004273:DNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; D014226:Triazenes; C022616:thiazolyl blue