A novel synthesis of dillapiol and its derivatives and their role as chemosensitizers and insecticide synergists.

Abstract

The present work summarizes the results of a study done by Dr Claude Bernard on the effect of the natural lignan, dillapiol, on multidrug resistance phenotypes. In a tissue culture system, dillapiol was selectively toxic to hamster drug-resistant B30 cells; this same compound was substantially less toxic to the drug-sensitive AUXB1 cell line. The so-called collateral sensitivity of drug-resistant tumor cells to an otherwise benign lignan compound makes dillapiol an ideal candidate for an adjuvant in chemotherapy. Examination of the toxicity of dillapiol revealed no negative effects with respect to weight changes or behavior of the rats, no deaths, and no abnormalities of the brain, liver, heart, kidney and lungs. Moreover, a drug-fate study using $\sp $C-radiolabeled dillapiol showed that the lignan is available to the liver, kidney and gut and is excreted almost entirely via the urine. A novel synthesis of dillapiol which allows the incorporation of $\sp $C radioactivity in the final product is also discussed. The preparation of several dillapiol derivatives from either the intermediates of the dillapiol synthesis or from the modification of dillapiol itself is presented. (Abstract shortened by UMI.)