Synthesis and cytotoxicity screening of substituted isobenzofuranones designed from anacardic acids.
This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.
Instituto de Química, Universidade de Brasília, Campus Darcy Ribeiro, Brasilia, Brazil.
Lúcio P L
LP
Logrado
Camila O
CO
Santos
Luiz A S
LA
Romeiro
Arinice M
AM
Costa
José R O
JR
Ferreira
Bruno C
BC
Cavalcanti
O
O
Manoel de Moraes
Letícia V
LV
Costa-Lotufo
Cláudia
C
Pessoa
Maria L
ML
Dos Santos
D048729:Anacardic Acids / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D010100:Oxygen / Q000737:chemistry
D048729:Anacardic Acids; D000970:Antineoplastic Agents; D001572:Benzofurans; C088115:anacardic acid; D010100:Oxygen