title: Synthesis and potent antitumor activity of new arylamino derivatives of nor-beta-lapachone and nor-alpha-lapachone.
abstract: Several arylamino derivatives of nor-beta-lapachone were synthesized in moderate to high yields and found to show very potent cytotoxicity against six neoplastic cancer cells: SF-295 (central nervous system), HCT-8 (colon), MDAMB-435 (breast), HL-60 (leukaemia), PC-3 (prostate), and B-16 (murine melanoma), with IC(50) below 1 microg/mL. Their cytotoxicities were compared to doxorubicin and with their synthetic precursors, beta-lapachone and nor-beta-lapachone. The activity against a normal murine fibroblast L-929 showed that some of the compounds were selective against cancer cells. The absence of hemolytic activity (EC(50)>200 microg/mL), performed with erythrocyte suspensions, suggests that the cytotoxicity of the compounds was not related to membrane damage of mouse erythrocytes. For comparison purposes, one isomeric compound based on nor-alpha-lapachone was also synthesized and showed lower activity than the related ortho-derivative. The modified arylamino quinones appear as interesting new lead compounds in anti-cancer drug development.
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Depto. de Química Orgânica, Campus do Valonguinho, 24020-150 Niterói, RJ, Brazil.
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva Júnior
authors.forename: Maria Cecília B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Antônio V
authors.initials: AV
authors.lastname: Pinto
authors.forename: Maria do Carmo F R
authors.initials: Mdo C
authors.lastname: Pinto
authors.forename: Marilia O F
authors.initials: MO
authors.lastname: Goulart
authors.forename: Francisco W A
authors.initials: FW
authors.lastname: Barros
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Manoel O
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship