Drug-induced porphyrin biosynthesis—XIV: Role of lipophilicity in determining porphyrin-inducing activity of esters and amides after blockade of their hydrolysis by bis-[ pnitrophenyl] phosphatex

Abstract

The porphyrin-inducing activity of a series of aromatic esters and amides was measured in chick embryo liver cells. Sterically unhindered aromatic esters which are inactive in the absence of a carboxylesterase inhibitor, bis-[ p-nitrophenyl]phosphate (BNPP), are markedly active in the presence of BNPP. On the other hand, the potency of Sterically hindered esters is similar in the presence and absence of BNPP. In contrast to the aromatic esters, both Sterically hindered and unhindered aromatic amides are active in the absence of BNPP. A high correlation was shown between porphyrin-inducing activity and lipophilicity of aromatic amides and esters after inhibition of aromatic ester hydrolysis by BNPP. It was concluded that porphyrin-inducing activity of aromatic esters and amides depends upon lipophilicity and resistance to rapid metabolism to compounds of lower lipophilicity.