Naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactones: antiproliferative activity and binding to bovine serum albumin and DNA.

A naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactone (methyl 2-[7-hydroxy-2-oxonaphtho[1,2-b]furan-3(2H)-yliden]acetate) has been prepared as a representative compound of a potential class of cytotoxic agents. In vitro cytotoxicity has been evaluated against HCT-15 colon and MCF-7 breast cancer cells and IC(50) was 64-66 μM, causing morphological changes in cells, such as loss of adhesion, rounding, cell shrinkage, and detachment from the substratum. The binding constant K of the complex between the naphthyl lactone with bovine serum albumin (8 × 10(3) M(-1)) suggests a minor change in protein folding. The K of the binding with DNA (1.06 × 10(4) M(-1)) suggests nonspecific electrostatic interactions with DNA and this was confirmed by melting point data (Tm<0.6 °C). Therefore, naphthalene-fused (α-alkoxycarbonyl)methylene-γ-butyrolactone should not be able to intercalate with DNA but its interaction should occur at the level of DNA surface.