ReviewDesign strategies of oxidosqualene cyclase inhibitors: Targeting the sterol biosynthetic pathway

- Targeting sterol biosynthesis pathway is an attractive strategy for drug discovery.
- Many oxidosqualene cyclase (OSC) inhibitors were designed based on the sterol scaffold.
- Novel structurally diverse inhibitors have been found by different approaches.
- OSC inhibitors are potential hypocholesterolemic, anticancer and antimicrobials.

Targeting the sterol biosynthesis pathway has been explored for the development of new bioactive compounds. Among the enzymes of this pathway, oxidosqualene cyclase (OSC) which catalyzes lanosterol cyclization from 2,3-oxidosqualene has emerged as an attractive target. In this work, we reviewed the most promising OSC inhibitors from different organisms and their potential for the development of new antiparasitic, antifungal, hypocholesterolemic and anticancer drugs. Different strategies have been adopted for the discovery of new OSC inhibitors, such as structural modifications of the natural substrate or the reaction intermediates, the use of the enzyme's structural information to discover compounds with novel chemotypes, modifications of known inhibitors and the use of molecular modeling techniques such as docking and virtual screening to search for new inhibitors. This review brings new perspectives on structural insights of OSC from different organisms and reveals the broad structural diversity of OSC inhibitors which may help evidence lead compounds for further investigations with various therapeutic applications.