Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs

Impacto

Downloads

Downloads per month over past year

Hoyos Vidal, Pilar and Pace, Vittorio and Alcántara León, Andrés Rafael (2019) Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs. Catalysts, 9 (3). p. 260. ISSN 2073-4344

[thumbnail of catalysts-09-00260.pdf] PDF
Creative Commons Attribution.

2MB

Official URL: https://doi.org/10.3390/catal9030260




Abstract

Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the largest selling class of drugs prescribed for the pharmacological treatment of hypercholesterolemia and dyslipidaemia. Statins also possess other therapeutic effects, called pleiotropic, because the blockade of the conversion of HMG-CoA to (R)-mevalonate produces a concomitant inhibition of the biosynthesis of numerous isoprenoid metabolites (e.g., geranylgeranyl pyrophosphate (GGPP) or farnesyl pyrophosphate (FPP)). Thus, the prenylation of several cell signalling proteins (small GTPase family members: Ras, Rac, and Rho) is hampered, so that these molecular switches, controlling multiple pathways and cell functions (maintenance of cell shape, motility, factor secretion, differentiation, and proliferation) are regulated, leading to beneficial effects in cardiovascular health, regulation of the immune system, anti-inflammatory and immunosuppressive properties, prevention and treatment of sepsis, treatment of autoimmune diseases, osteoporosis, kidney and neurological disorders, or even in cancer therapy. Thus, there is a growing interest in developing more sustainable protocols for preparation of statins, and the introduction of biocatalyzed steps into the synthetic pathways is highly advantageous—synthetic routes are conducted under mild reaction conditions, at ambient temperature, and can use water as a reaction medium in many cases. Furthermore, their high selectivity avoids the need for functional group activation and protection/deprotection steps usually required in traditional organic synthesis. Therefore, biocatalysis provides shorter processes, produces less waste, and reduces manufacturing costs and environmental impact. In this review, we will comment on the pleiotropic effects of statins and will illustrate some biotransformations nowadays implemented for statin synthesis.


Item Type:Article
Uncontrolled Keywords:biocatalysis; biotransformations; statins; pleiotropic effects
Subjects:Medical sciences > Pharmacy > Pharmaceutical chemistry
ID Code:67097
Deposited On:29 Jul 2021 14:25
Last Modified:17 Aug 2021 07:15

Origin of downloads

Repository Staff Only: item control page