Rational design, synthesis and structure–activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones

Novel substituted 6,7-dimethoxy-1-tetralones and 5,6-dimethoxy-1-indanones have been synthesized and evaluated for their cytotoxicity. Compounds with 3′-lipophilic, 3′,5′-dilipophilic, or 3′,5′-dilipophilic-4′-hydrophilic substituents on (E)-2-benzylidene moiety showed highly cytotoxic effects. The unique structure of 42 possibly matches the pharmacophore features for these cytotoxic compounds.