Structural Analogues of Lanosterol from Marine Organisms of the Class Asteroidea as Potential Inhibitors of Human and Candida albicans Lanosterol 14α-demethylases

Abstract

Lanosterol 14α-demethylases (hemoproteins of the cytochrome P450(51) family) are involved in biosynthesis of different membrane sterols, including animal cholesterol, fungal ergosterol and C24-modified plant and protozoa sterols. In this study we have investigated 10 structural analogs of lanosterol isolated from echinoderms belonging to the class Asteroidea as potential ligands (competitive inhibitors) of human and Candida albicans cytochromes P450(51). The study was performed using the surface plasmon resonance method, spectrophotometric titration and enzyme assay. Among the compounds tested we found several selective ligands for human and Candida albicans cytochromes. Between selective ligands of the human lanosterol 14α-demethylase we found two novel inhibitors of this enzyme: henricioside H₁ and levisculoside G from Henricia derjugini. With due consideration of obtained data, we conclude that marine organisms from the class Asteroidea can be a valuable source of new lead compounds for creation of selective inhibitors of cytochromes P450(51) family with less side effects due to their selective action on these enzymes in different types of organisms.