Document Type: Review Article

Authors

1 Department of Chemistry, Iran University of Science and Technology, Tehran, Iran

2 Department of Chemical Engineering, Payame Noor University, Tehran, Iran

3 Department of Physical Chemistry, Alzahra University, Tehran, Iran

10.33945/SAMI/JCR.2020.1.1

Abstract

Cardiovascular disease (CVD) represents one of the most important health problems. One of the main risk factors for CVD death is the high cholesterol levels. Statins have been shown to lower low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular disease, and are currently the first line of treatment for hypercholesterolemia. Atorvastatin is one of the most effective drugs and is part of the blood lipid lowering drug group. This work studies the mechanism of the use of statin family drugs and atorvastatin to determine the clinical requirements for improving the dermatology and the statins.

Graphical Abstract

Keywords

[1] Winslow, R. (2000). Birth of a blockbuster: Lipitor’s unlikely route out of the lab. Wall Street Journal24.

[2] Endo, A. (1992). The discovery and development of HMG-CoA reductase inhibitors. Journal of lipid research33(11), 1569-1582.

[3] Rosa, G. M., Carbone, F., Parodi, A., Massimelli, E. A., Brunelli, C., Mach, F., ... & Montecucco, F. (2014). Update on the efficacy of statin treatment in acute coronary syndromes. European journal of clinical investigation44(5), 501-515.

[4] Hongbao, M., & Yan, Y. Streptozotocin, Atorvastatin, Renal, Diabetes and Related Factors.

[5] Adams, S. P., Tsang, M., & Wright, J. M. (2012). Lipid lowering efficacy of atorvastatin. Cochrane database of systematic reviews, (12).

[6] Hermann, M., Bogsrud, M. P., Molden, E., Åsberg, A., Mohebi, B. U., Ose, L., & Retterstøl, K. (2006). Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several‐fold in patients with atorvastatin‐induced myopathy. Clinical Pharmacology & Therapeutics79(6), 532-539.

[7] Christians, U., Jacobsen, W., & Floren, L. C. (1998). Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar?. Pharmacology & therapeutics80(1), 1-34.

[8] Tobert, J. A. (2003). Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nature reviews Drug discovery2(7), 517.

[9] Macedo, A. F., Taylor, F. C., Casas, J. P., Adler, A., Prieto-Merino, D., & Ebrahim, S. (2014). Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC medicine12(1), 51.

[10] Roche, V. F. (2005). Antihyperlipidemic statins: a self-contained, clinically relevant medicinal chemistry lesson. American Journal of Pharmaceutical Education69(4), 77.

[11] Istvan, E. S., & Deisenhofer, J. (2001). Structural mechanism for statin inhibition of HMG-CoA reductase. Science292(5519), 1160-1164.

[12] Shepherd, J., Hunninghake, D. B., Barter, P., McKenney, J. M., & Hutchinson, H. G. (2003). Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals. The American journal of cardiology91(5), 11-17.

[13] Liu, J., Zhang, J., Shi, Y., Grimsgaard, S., Alraek, T., & Fønnebø, V. (2006). Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chinese medicine1(1), 4.

[14] Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crécy-Lagard, V., & Osterman, A. (2002). Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. Journal of Biological Chemistry277(24), 21431-21439.

[15] Bachhawat, B. K., Austin, J., & Armstrong, D. (2015). A Cerebroside Sulphotransferase Deficiency in a Human Disorder of Myelin. The National medical journal of India28(3), 161-164.

[16] Surolia, A. (1997). An outstanding scientist and a splendid human being: Prof Bimal Kumar Bachhawat. Glycobiology7(4), R5-R6.

[17] Stancu, C., & Sima, A. (2001). Statins: mechanism of action and effects. Journal of cellular and molecular medicine5(4), 378-387.

[18] Puccetti, L., Pasqui, A. L., Pastorelli, M., Bova, G., Cercignani, M., Palazzuoli, A., ... & Bruni, F. (2002). Time‐dependent effect of statins on platelet function in hypercholesterolaemia. European journal of clinical investigation32(12), 901-908.

[19] Roth, B. D. (2002). 1 The Discovery and Development of Atorvastatin, a Potent Novel Hypolipidemic Agent. In Progress in medicinal chemistry (Vol. 40, pp. 1-22). Elsevier.

[20] Miziorko, H. M. (2011). Enzymes of the mevalonate pathway of isoprenoid biosynthesis. Archives of biochemistry and biophysics505(2), 131-143.

[21] Frantz Jr, I. D., & Schroepfer Jr, G. J. (1967). Sterol biosynthesis. Annual review of biochemistry36(1), 691-726.

[22] Hosokawa, G., Patterson, G. W., & Lusby, W. R. (1984). Effects of triarimol, tridermorph and triparanol on sterol biosynthesis in carrot, tobacco and soybean suspension cultures. Lipids19(6), 449-456.

[23] Singh, P., Saxena, R., Srinivas, G., Pande, G., & Chattopadhyay, A. (2013). Cholesterol biosynthesis and homeostasis in regulation of the cell cycle. PloS one8(3), e58833.

[24] BEYER, R. S., & JENSEN, L. S. (1993). The hypocholesterolemic agent dichloroacetate increases egg cholesterol content of laying hens. Poultry science72(6), 1063-1069.

[25] Boots, M. R., Boots, S. G., Noble, C. M., & Guyer, K. E. (1973). Hypocholesterolemic Agents II: Inhibition of β-Hydroxy-β-methylglutaryl Coenzyme A Reductase by Arylalkyl Hydrogen Succinates and Glutarates. Journal of pharmaceutical sciences62(6), 952-957.

[26] Brown, A. G., Smale, T. C., King, T. J., Hasenkamp, R., & Thompson, R. H. (1976). Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum. Journal of the Chemical Society, Perkin Transactions 1, (11), 1165-1170.

[27] Endo, A., Tsujita, Y., Kuroda, M., & TANZAWA, K. (1977). Inhibition of Cholesterol Synthesis in vitro and in vivo by ML‐236A and ML‐236B, Competitive Inhibitors of 3‐Hydroxy‐3‐methylglutaryl‐Coenzyme A Reductase. European Journal of Biochemistry77(1), 31-36.

[28] Alberts, A. W., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., ... & Patchett, A. (1980). Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proceedings of the National Academy of Sciences77(7), 3957-3961.

[29] Endo, A. (1979). Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. The Journal of antibiotics32(8), 852-854..

[30] Hoffman, W. F., Alberts, A. W., Anderson, P. S., Chen, J. S., Smith, R. L., & Willard, A. K. (1986). 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side-chain ester derivatives of mevinolin. Journal of medicinal chemistry29(5), 849-852.

[31] Paal, C. (1885). Synthese von Thiophen‐und Pyrrolderivaten. Berichte der deutschen chemischen Gesellschaft18(1), 367-371.

[32] Narasaka, K., & Pai, H. C. (1980). Stereoselective synthesis of meso (or erythro) 1, 3-diols from β-hydroxyketones. Chemistry Letters9(11), 1415-1418.

[33] Rádl, S., Stach, J., & Hajicek, J. (2002). An improved synthesis of 1, 1-dimethylethyl 6-cyanomethyl-2, 2-dimethyl-1, 3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis. Tetrahedron letters43(11), 2087-2090.

[34] Bodurow, C. C., Boyer, B. D., Brennan, J., Bunnell, C. A., Burks, J. E., Carr, M. A., ... & Graves, B. J. (1989). An enantioselective synthesis of loracarbef (LY163892/KT3777). Tetrahedron Letters30(18), 2321-2324.

[35] Hu, F. B., Stampfer, M. J., Manson, J. E., Rimm, E., Colditz, G. A., Rosner, B. A., ... & Willett, W. C. (1997). Dietary fat intake and the risk of coronary heart disease in women. New England journal of medicine337(21), 1491-1499.

[36] Chen, K. M., Hardtmann, G. E., Prasad, K., Repič, O., & Shapiro, M. J. (1987). 1, 3-syn diastereoselective reduction of β-hydroxyketones utilizing alkoxydialkylboranes. Tetrahedron letters28(2), 155-158.

[37] Kumar, P., Deshmukh, A. N., Upadhyay, R. K., & Gurjar, M. K. (2005). A simple and practical approach to enantiomerically pure (S)-3-hydroxy-γ-butyrolactone: synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester. Tetrahedron: Asymmetry16(16), 2717-2721.

[38] Pfruender, H., Amidjojo, M., Hang, F., & Weuster-Botz, D. (2005). Production of Lactobacillus kefir cells for asymmetric synthesis of a 3, 5-dihydroxycarboxylate. Applied microbiology and biotechnology67(5), 619-622.

[39] Patel, R. N., Banerjee, A., McNamee, C. G., Brzozowski, D., Hanson, R. L., & Szarka, L. J. (1993). Enantioselective microbial reduction of 3, 5-dioxo-6-(benzyloxy) hexanoic acid, ethyl ester. Enzyme and microbial technology15(12), 1014-1021.

[40] Wolberg, M., Hummel, W., Wandrey, C., & Müller, M. (2000). Highly regio‐and enantioselective reduction of 3, 5‐dioxocarboxylates. Angewandte Chemie International Edition39(23), 4306-4308.

[41] Gijsen, H. J., & Wong, C. H. (1994). Unprecedented asymmetric aldol reactions with three aldehyde substrates catalyzed by 2-deoxyribose-5-phosphate aldolase. Journal of the American Chemical Society116(18), 8422-8423.

[42] Liu, J., Hsu, C. C., & Wong, C. H. (2004). Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin. Tetrahedron letters45(11), 2439-2441.

[43] Greenberg, W. A., Varvak, A., Hanson, S. R., Wong, K., Huang, H., Chen, P., & Burk, M. J. (2004). Development of an efficient, scalable, aldolase-catalyzed process for enantioselective synthesis of statin intermediates. Proceedings of the National Academy of Sciences101(16), 5788-5793.

[44] DeSantis, G., Zhu, Z., Greenberg, W. A., Wong, K., Chaplin, J., Hanson, S. R., ... & Robertson, D. E. (2002). An enzyme library approach to biocatalysis: development of nitrilases for enantioselective production of carboxylic acid derivatives. Journal of the American Chemical Society124(31), 9024-9025.

[45] DeSantis, G., Wong, K., Farwell, B., Chatman, K., Zhu, Z., Tomlinson, G., ... & Kretz, K. (2003). Creation of a productive, highly enantioselective nitrilase through gene site saturation mutagenesis (GSSM). Journal of the American Chemical Society125(38), 11476-11477.

[46] Short, J. M. (2001). U.S. Patent No. 6,171,820. Washington, DC: U.S. Patent and Trademark Office.

[47] Bergeron, S., Chaplin, D. A., Edwards, J. H., & Ellis, B. S. (2006). W., Hill CL, Holt-Tiffin K., Knight JR, Mahoney T., Osborne AP, Ruecroft G. Org. Proc. Res. Dev10, 661.

[48] Sun, F., Xu, G., Wu, J., & Yang, L. (2006). Efficient lipase-catalyzed kinetic resolution of 4-arylmethoxy-3-hydroxybutanenitriles: application to an expedient synthesis of a statin intermediate. Tetrahedron: Asymmetry17(20), 2907-2913.

[49] Wang, G., & Hollingsworth, R. I. (1999). Synthetic routes to L-carnitine and L-gamma-amino-beta-hydroxybutyric acid from (S)-3-hydroxybutyrolactone by functional group priority switching. Tetrahedron: Asymmetry10(10), 1895-1901.

[50]  Lee, S. H., Park, O. J., & Uh, H. S. (2008). A chemoenzymatic approach to the synthesis of enantiomerically pure (S)-3-hydroxy-γ-butyrolactone. Applied microbiology and biotechnology79(3), 355-362.

[51] Goldberg, S., Guo, Z., Chen, S., Goswami, A., & Patel, R. N. (2008). Synthesis of ethyl-(3R, 5S)-dihydroxy-6-benzyloxyhexanoates via diastereo-and enantioselective microbial reduction: Cloning and expression of ketoreductase III from Acinetobacter sp. SC 13874. Enzyme and Microbial Technology43(7), 544-549.

[52] Majerić Elenkov, M., Tang, L., Hauer, B., & Janssen, D. B. (2006). Sequential kinetic resolution catalyzed by halohydrin dehalogenase. Organic letters8(19), 4227-4229.

[53] Patel, J. M. (2009). Biocatalytic synthesis of atorvastatin intermediates. Journal of Molecular Catalysis B: Enzymatic61(3-4), 123-128.

[54] Hu, L., Xiong, F., Chen, X., Chen, W., He, Q., & Chen, F. (2013). Synthetic studies on statins. Part 1: a short and cyanide-free synthesis of atorvastatin calcium via an enantioselective aldol strategy. Tetrahedron: Asymmetry24(4), 207-211.

[55] Su, Z., Wen, J., Dente, L., Velde, R. V. D., Wang, L., Ma, Y., ... & Hu, Z. (2011). The Tibetan Plateau observatory of plateau scale soil moisture and soil temperature (Tibet-Obs) for quantifying uncertainties in coarse resolution satellite and model products. Hydrology and earth system sciences15(7), 2303-2316.

[56] Brower, P. L., Butler, D. E., Deering, C. F., Le, T. V., Millar, A., Nanninga, T. N., & Roth, B. D. (1992). The synthesis of (4R-cis)-1, 1-dimethylethyl 6-cyanomethyl-2, 2-dimethyl-1, 3-dioxane-4-acetate, a key intermediate for the preparation of CI-981, a highly potent, tissue selective inhibitor of HMG-CoA reductase. Tetrahedron Letters33(17), 2279-2282.

[57] Trost, B. M., & Brindle, C. S. (2010). The direct catalytic asymmetric aldol reaction. Chemical Society Reviews39(5), 1600-1632.

[58] Liuzzo, G., Biasucci, L. M., Gallimore, J. R., Grillo, R. L., Rebuzzi, A. G., Pepys, M. B., & Maseri, A. (1994). The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. New England journal of medicine331(7), 417-424.

[59] Narasaka, K., & Pai, F. C. (1984). Stereoselective reduction of β hydroxyketones to 1, 3-diols highly selective 1, 3-asymmetric induction via boron chelates. Tetrahedron40(12), 2233-2238.

[60] Black, D. M., Bakker-Arkema, R. G., & Nawrocki, J. W. (1998). An overview of the clinical safety profile of atorvastatin (Lipitor), a new HMG-CoA reductase inhibitor. Archives of internal Medicine158(6), 577-584.

[61] Maron, D. J., Fazio, S., & Linton, M. F. (2000). Current perspectives on statins. Circulation101(2), 207-213.

[62] Rosenson, R. S. (2004). Statins: can the new generation make an impression?. Expert opinion on emerging drugs9(2), 269-279.

[63] Ballantyne, C. M. (1998). Low-density lipoproteins and risk for coronary artery disease. The American journal of cardiology82(8), 3-12.

[64] Olsson, A. G., Pauciullo, P., Soska, V., Luley, C., Pieters, R. E., Broda, G., ... & Fluvastatin Study Group. (2001). Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial. Clinical therapeutics23(1), 45-61.

[65] Toth, P. P., Worthy, G., Gandra, S. R., Sattar, N., Bray, S., Cheng, L. I., ... & Deshpande, S. (2017). Systematic review and network meta‐analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia. Journal of the American Heart Association6(10), e005367.