Molecular Pharmacology, Vol 20, 206-210, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Studies of the Porphyrin-Inducing Activity of Ethynyl Compounds and Conformationally Restricted and Unrestricted Analogues of Allylisopropylacetamide in Chick Embryo Liver Cell Culture

¹ Department of Pharmacology, Queen's University, Kingston, Ontario, Canada, K7L 3N6, and Department of Pharmaceutical Chemistry, School of Pharmacy and Liver Center, University of California, San Francisco, California 94143

A series of conformationally restricted and unrestricted analogues of allylisopropylacetamide (AIA) and a group of ethynyl compounds have been tested for porphyrin-inducing activity in chick embryo liver cell culture. The conformationally restricted analogues, which do not share the ability of AIA to destroy rat and chick embryo hepatic cytochrome P-450, were nevertheless shown to induce porphyrin accumulation. The conformationally unrestricted analogues and the ethynyl compounds which do share the ability of AIA to destroy rat hepatic cytochrome P-450 possessed weak to moderate porphyrin-inducing activity or were inactive. It is concluded that in chick embryo liver cell culture, in contrast to the situation in rat liver, destruction of the heme moiety of cytochrome P-450 does not appear to be a prerequisite for -aminolevulinic acid synthetase induction and porphyrin accumulation.