Synthesis and evaluation of quinonoid compounds against tumor cell lines.
Thirty two compounds were synthesized in moderate to high yields and showed activity against cancer cells HL-60 (leukemia), MDA-MB435 (melanoma), HCT-8 (colon) and SF295 (central nervous system), with IC(50) below 2 μM for some compounds. The β-lapachone-based 1,2,3-triazoles showed the best cytoxicity profile and emerge as promising anticancer prototypes. Insights about the reactive oxygen species (ROS) mechanism of anticancer action for some compounds were obtained by addition of 1-bromoheptane that deplete reduced glutathione (GSH) content and by using N-acetylcysteine that protects cells against apoptotic cellular death, as well by analysis of thiobarbituric acid reactive substances (TBARS) formation, and oxidative DNA damage after treatment detected by the comet assay with the bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (ENDOIII).
Núcleo de Pesquisas de Produtos Naturais, UFRJ, 21941-971, Rio de Janeiro, RJ, Brazil. eufranio.junior@yahoo.com.br
Eufrânio N
EN
da Silva
Bruno C
BC
Cavalcanti
Tiago T
TT
Guimarães
Maria do Carmo F R
Mdo C
Pinto
Igor O
IO
Cabral
Cláudia
C
Pessoa
Letícia V
LV
Costa-Lotufo
Manoel O
MO
de Moraes
Carlos K Z
CK
de Andrade
Marcelo R
MR
Dos Santos
Carlos A
CA
de Simone
Marilia O F
MO
Goulart
Antonio V
AV
Pinto
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053960:DNA Breaks / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50
D000970:Antineoplastic Agents; D016227:Benzoquinones; C004532:quinone