Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds - A Review

Studies on the various cholesterol-lowering agents is one of the important areas in clinical research. Identifica- tion and characterization of potential molecules from various sources have been carried out in the past and their relation- ship with the enzymes which are involved in the cholesterol cascade is gaining interest. In this review, we have high- lighted various inhibitors involved in the cholesterol cascade as well as cholesterol-lowering agents, viz., tocotrienol, flavonoids, phytosterols, phytostanols, statins, DADS, and synthetic compounds. The mechanism of action and characteri- zation of these hypocholesterolemic compounds are discussed in this communication. Major natural sources as well as synthetic and biological routes of synthesis of these compounds are reviewed in a concise manner. Especially, various HMG-CoA analogues including statins have been reviewed specifically. In this respect, researchers have identified 2,3- oxidosqualene cyclase-lanosterol synthase (lanosterol syn- thase, oxidosqualene-lanosterol cyclase, lanosterol synthase, 2,3-oxidosqualene-lanosterol cyclase, human lanosterol syn- thase (EC 5.4.99.7)) having a molecular weight of 83 kDa, catalyzing the highly selective cyclization reaction from the substrate 2,3-oxidosqualene (squalene 2,3-epoxide, squalene 2,3-oxide, (S)-squalene-2,3-epoxide, 2,3-epoxisqualene, oxidosqualene) into lanosterol, as an appropriate step for the inhibition of cholesterol biosynthesis (3). Oxidosqualene cyclase inhibitors (OSCI) arrest the downstream of 2,3- oxidosqualene which helps to stimulate epoxysterols to