Cholesterol-lowering drugs, structure

The cholesterol-lowering drug atorvastatin, marketed as Lipitor, is an example where biocatalysis research has been applied extensively and is in industrial use. The enzyme 2-deoxyribose-5-phosphate aldolase (DERA) has been a target of directed evolution for the production of atorvastatin intermediates [8,9,71]. DeSantis and coworkers [8,9] used structure-based... 

Probucol (4,4/-[(l-methylethylidene)bis(thio)]-bis-[2,6-bis(l,l-dime-thylethyl)phenol]) is a cholesterol-lowering drug that has been reported to exist in two forms [27]. Form II has been found to exhibit a lower melting point onset relative to Form I, and samples of Form II spontaneously transform to Form I upon long-term storage. The structures of these two polymorphic forms have been reported, and a summary of the crystallographic data obtained in this work is provided in... 

Structural similarity of HMG and simvastatin, a clinically useful cholesterol-lowering drug of the statin" family. 

Gerber, J.J. Caira, M.R. Letter, A.P. Structures of two conformational polymorphs of the cholesterol-lowering drug probucol. J. Cryst. Spect. Res. 1993, 23, 863-869. 

Fig. 3. Chemical structures of HMG-CoA and several statin inhibitors of HMG-CoA reductase. Atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) are widely prescribed cholesterol-lowering drugs.

Ito, S., T. Hata, 1. Watanabe, T. Matsuoka, and N. Serizawa (1997). Crystal structure of cytochrome P450sca from Streptomyces carbophilus involved in production of pravastatin, a cholesterol lowering drug. FASEBJ. 11, 36. 

The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

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