Drug-induced porphyrin biosynthesis-XVII. Evaluation of the porphyrin-inducing activity of aliphatic mono- and diesters before and after bis( p-nitrophenyl) phosphate treatment of chick embryo liver cells

Abstract

The porphyrin-inducing activity of a series of aliphatic mono- and diesters was measured in chick embryo liver cells. Sterically unhindered diesters, which are inactive in the absence of a carboxylesterase inhibitor, bis-( p-nitrophenyl) phosphate (BNPP), are markedly active in the presence of BNPP. Sterically hindered diesters do not require pretreatment with BNPP to exhibit activity, but show greater potency in its presence. After BNPP pretreatment, the potency of diesters paralleled their lipophilicity, supporting the conclusion that porphyrin-inducing activity of esters and amides depends upon lipophilicity and resistance to rapid metabolism to compounds of lower lipophilicity. Aliphatic monoesters were found to be inactive; moreover, in contrast to diesters, they remained inactive after BNPP pretreatment. The inactivity of monoesters after BNPP pretreatment could not be attributed to hydrolysis by BNPP-insensitive microsomal or lysosomal esterases, but was found to be the result of evaporation of these compounds from the surface of the culture medium in which the cells were incubated.