ABSTRACT
Searching for enzyme inhibitors is a rational and efficient approach to drug discovery. The enzymatic cyclization of 2,3-oxidosqualene to tetra- or pentacyclic triterpenes may be ideally separated into three distinct steps: acid-catalyzed opening of the epoxide ring; concerted or not concerted cyclization to give a tetra- or pentacyclic carbonium ion; the concerted backbone rearrangement to lanosterol, cycloartenol or similar tetra- or pentacyclic triterpenes. Synthesis and study of the biological action of new site-directed irreversible 2,3-oxidosqualene cyclase (OSC) inhibitors may help to understand the enzyme’s structure and mechanism of action. The internal site can potentially interfere in each step of OS transformation: initial protonation, cyclization and the following rearrangement, and the final removal of a proton that leads to the final product. Oxidosqualene cyclase is associated with the endoplasmic reticulum in eukaryotic cells. Several OSC have been purified to homogeneity from vertebrate, plant and yeast sources.
