Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor
Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically
produced from the fungus Aspergillus terreus and has a high log p value (log p = 4.39)and thus
high hepatic extraction and high efficacy in controlling cholesterol synthesis. The current study
was undertaken to investigate the metabolic profile of SV using various mass spectrometry (MS)
platforms. Metabolic profiling was studied in in vitro models, rat liver microsomes (RLMs), and
isolated perfused rat liver hepatocytes (RLHs) using both ion trap and triple quadruple LC–MS/MS
systems. A total of 29 metabolites were identified. Among them, three types of SV-related phase-I
metabolites, namely exomethylene simvastatin acid (exomethylene SVA), monohydroxy SVA, and
dihydrodiol SVA, were identified as new in RLMs. No phase-II metabolites were identified while
incubating with RLHs
Cancer remains the leading cause of human morbidity universally. Hence, we
sought to assess the in vitro antiproliferative activity of new isatin-based conjugates (5a–s)
against three…
Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically
produced from the fungus Aspergillus terreus and has a high log p value (log p = 4.39)and thus…
Simvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering
drug. Here, the detection and characterization of SV and its metabolites was studied in…