3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives: synthesis and cytotoxicity against cancer cell lines

Eufrânio N da Silva Jr; Clara F de Deus; Bruno C Cavalcanti; Cláudia Pessoa; Letícia V Costa-Lotufo; Raquel C Montenegro; Manoel O de Moraes; Maria do Carmo F R Pinto; Carlos A de Simone; Vitor F Ferreira; Marilia O F Goulart; Carlos Kleber Z Andrade; Antônio V Pinto

doi:10.1021/jm900865m

3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives: synthesis and cytotoxicity against cancer cell lines

J Med Chem. 2010 Jan 14;53(1):504-8. doi: 10.1021/jm900865m.

Authors

Eufrânio N da Silva Jr¹, Clara F de Deus, Bruno C Cavalcanti, Cláudia Pessoa, Letícia V Costa-Lotufo, Raquel C Montenegro, Manoel O de Moraes, Maria do Carmo F R Pinto, Carlos A de Simone, Vitor F Ferreira, Marilia O F Goulart, Carlos Kleber Z Andrade, Antônio V Pinto

Affiliation

¹ Instituto de Quimica, Universidade de Brasilia, 70910-970 Brasilia, DF, Brazil.

PMID: 19947600
DOI: 10.1021/jm900865m

Abstract

Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimethoxy substituted naphthoquinones showed the best cytoxicity profile, while the ortho-nitro and the 2,4-dimethoxy substituted ones were more selective than doxorubicin and similar to the precursor lapachones, thus emerging as promising new lead compounds in anticancer drug development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation / drug effects
Crystallography, X-Ray
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Naphthoquinones / chemical synthesis*
Naphthoquinones / chemistry
Naphthoquinones / pharmacology*
Naphthoquinones / toxicity
Stereoisomerism
Structure-Activity Relationship

Substances

Naphthoquinones
beta-lapachone