Synthesis of New Dehydrodieugenol Derivatives via Olefin Cross Metathesis and In Vitro Evaluation of Their Trypanocidal Activity

Ruthenium-catalyzed cross metathesis using biseugenol (1) with electron-deficient olefins methyl (2a) and ethyl (2b) acrylates, acrylic acid (2c), acrylonitrile (2d), and methyl methacrylate (2e) derivatives have been conducted to afford respective derivatives 3a-3e with good yields and excellent conversion rates. Activity of prepared compounds against trypomastigote and amastigote forms of Trypanosoma cruzi and mammalian cytotoxicity have been evaluated. The results obtained indicate that the IC50 values for amastigotes of compounds 3b and 3d are quite similar to those of biseugenol (1), but unlike this compound, they show reduced toxicities with SI values similar to those of the standard drug benznidazol.

Automated summary

Ruthenium-catalyzed cross metathesis of biseugenol with electron-deficient olefins resulted in the synthesis of derivatives 3a-3e in good yields and excellent conversion rates. The antitrypanosomal activity of these compounds against Trypanosoma cruzi was evaluated, and compounds 3b and 3d showed similar IC50 values to biseugenol, but with reduced toxicities and similar selectivity indexes to the standard drug benznidazol.