Synthesis of the first unnatural schisantherins and their effects in multidrug-resistant cancer cells

Schisandrol A, a dibenzocyclooctadiene lignan, was obtained by a simplified procedure from Schisandra chinensis fruits. Its reaction with carboxylic acids to give new esters (schisantherins) required special conditions such as microwave irradiation. An X-ray single crystal structure analysis of schisandrol A revealed a sterical shielding of the secondary OH group as the likely reason. The cinnamoate inhibited the P-gp drug transporters of multidrug-resistant human Kb-V1 cervix carcinoma cells better than the natural benzoate and comparable to the clinical sensitizer verapamil.