X-ray structural analysis and antitumor activity of new salicylic acid derivatives

Abstract

© 2014 Springer Science+Business Media New York. Tetrakis-, tris-, bis-, and mono salicylic acid derivatives 1-4 were synthesized by reaction of methyl 2-hydroxy benzoate (methyl salicylate) with 2,2-bis (hydroxymethyl) propane-1,3-diol (pentaerythritol) in the presence of sodium. Yields of different salicyloyloxy derivatives were changed by varying the molar ratios of reactants. For compounds 2 and 3, X-ray structure analysis was performed, as well as molecular energy minimization, to define their conformation in terms of their energy minima. Comparison of crystal and energy minimized structures for these two compounds (2 and 3) revealed that the intramolecular hydrogen bonds play an important role, stabilizing conformation of the most part of the molecule. The antioxidant activity and cytotoxicity of the synthesized derivatives were evaluated in a series of in vitro tests, as well as 17β-hydroxysteroid dehydrogenase type 2 inhibition potency. Tetrakis salicyloyloxy derivative 1 expressed the highest antioxidant potency, tris salicyloyloxy derivative 2 was the best inhibitor of 17βHSD2 enzyme, while bis salicyloyloxy derivative 3 showed strong cytotoxicity against prostate and breast cancer cells with no cytotoxicity against healthy cells.