1. Academic Validation
  2. Synthesis and potent antitumor activity of new arylamino derivatives of nor-beta-lapachone and nor-alpha-lapachone

Synthesis and potent antitumor activity of new arylamino derivatives of nor-beta-lapachone and nor-alpha-lapachone

  • Bioorg Med Chem. 2007 Nov 15;15(22):7035-41. doi: 10.1016/j.bmc.2007.07.043.
Eufrânio N da Silva Júnior 1 Maria Cecília B V de Souza Antônio V Pinto Maria do Carmo F R Pinto Marilia O F Goulart Francisco W A Barros Claudia Pessoa Letícia V Costa-Lotufo Raquel C Montenegro Manoel O de Moraes Vitor F Ferreira
Affiliations

Affiliation

  • 1 Universidade Federal Fluminense, Instituto de Química, Depto. de Química Orgânica, Campus do Valonguinho, 24020-150 Niterói, RJ, Brazil.
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.

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