1. Invest New Drugs. 2010 Mar 17. [Epub ahead of print]

An in vitro comparative study with furyl-1,4-quinones endowed with anticancer
activities.

Benites J, Valderrama JA, Taper H, Buc Calderon P.

Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat,
Iquique, Chile, Avenida Arturo Prat 2120, Casilla 121, Iquique, Chile.

We describe the biological activity of some furylbenzo- and naphthoquinones
(furylquinones) on hepatocarcinoma cells and healthy rat liver slices. The
effects of furylquinones on cancer cells (Transplantable Liver Tumor, TLT) were
assessed by measuring cell death (membrane cell lysis); intracellular contents of
ATP and GSH and the activity of caspase-3 were used to determine the type of cell
death. Most of the furylquinones tested (at a concentration of 25 mug/ml) induced
caspase-independent cell death but compound 4 had no cytotoxic effects. The
levels of both ATP and GSH were severely affected by quinones 1, 2 and 5, while
no effect was observed with compound 4. These cytotoxic properties of quinones
are associated with physico-chemical properties as shown by the LUMO energies and
lipophilicity. Interestingly, no cytotoxic effects of furylquinones were detected
when the in vitro model of precision-cut liver slices (PCLS) was used. Indeed,
although CYP2E1 activity was slightly affected, ATP and GSH levels as well as
protein synthesis were not modified by furylquinones. Paracetamol, a well-known
hepatotoxicant, reduced these parameters by more than 80% compared to control
conditions. Taking into account the considerable incidence of adverse-effects
induced by most current anticancer drugs, the selective cytotoxicity shown by
compounds 1, 2 and 5, in particular that of 1, represents a safety factor that
encourages the further development of these quinones as new drugs in cancer
therapy.

PMID: 20237828 [PubMed - as supplied by publisher]