Unnatural prostaglandins of biochemical and physiological significance

Abstract

Some artificial prostaglandins (PGs) synthesized by the three-component process possess significant biological properties. Isocarbacyclin, a stable analogue of PGI2, is a promising agent for the treatment of various thrombotic diseases. 19-(3-Azidophenyl)-20-norisocarbacyclin (APNIC) has a sufficiently high affinity to the prostacyclin receptor protein in mastocytoma P-815 cells, exhibiting an IC50 value of 3 nM for the replacement of iloprost. Photoaffinity labeling experiments using 15-tritium-labeled APNIC have resulted in the characterization of the PGI2 receptor protein. Δ7-PGA1 methyl ester exhibits unique anti-tumor and anti-viral activities independent of cAMP levels. The dienone PGs are transported reversibly into cultured L1210 leukemia cells and then accumulate in nuclei via covalent interaction, eliciting growth inhibition. This cellular behavior is well correlated with the chemical behavior in the presence of thiols. The dienone undergoes a reversible Michael reaction with various thiols in the homogeneous phase, whereas the reaction with polymer-anchored thiols occurs in an irreversible manner. PGA1 methyl ester, a less potent enone PG, reacts with thiols at a lower rate, but the resulting adducts are more stable than the dienone adducts. © 1994 IUPAC