Synthesis and Spectroscopic Characterization of Metal Complexes of Rosuvastatin

Abstract

Context: Rosuvastatin is a cholesterol lowering drug. It belongs to class statin. It is prescribed to the patients of coronary artery disease; atherosclerosis; thrombosis; increased low-density-lipoprotein; lipid and triglyceride. Aims:It is a newer drug in market and studies over the pharmacodynamics and pharmacokinetics are in progress. Statin therapy is a long term treatment for which its behavior in the presence of other agents is necessary. For this purpose present study is based on the interaction of the drug with essential and trace elements present in human body or co-administered during multivitamin therapy. Settings and Design: Complexes of rosuvastatin with Cd(II), Cr(II), Mn(II), Fe(III), Co(II), Ni(II) and Zn(II) i.e., metals commonly present in multivitamins, were synthesized in laboratory. Methanolic solution of rosuvastatin with metal chloride salts was reacted. Methods and Material: Reaction between drug and metals was carried out in thermostat at 80 o C for five hours with timely TLC monitoring for completion of reaction. These newly synthesized complexes were identified by IR and NMR spectroscopy and CHN elemental microanalysis and the structure of complexes was proposed. Results: Analyses suggest two molecules of rosuvastatin co-ordinate with the central metal atom through their carboxylic group. CS Chem3D ultra suggests square planner structure of the complex. Conclusions: Synthesis of compounds proposes that rosuvastatin can bind to metals as ligand through its pharmocophore site that may lead to reduced activity of drug and metal both. The study is precursor to in vitro and in vivo study of interaction of drug and metals.

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“…The results of the present study revealed that metformin and rosuvastatin decreased the levels of TBARS with an increase in the levels of GSH and thus demonstrated a significant in-vitro antioxidant effect with a possible beneficial effect in SCD. The antioxidant effects of metformin and rosuvastatin could be attributed to direct free radical scavenging activities, particularly hydroxyl radicals 17,18 , or to binding ability with metals like iron and copper 19,20 . H 2 O 2 in the presence of metal ions can be broken down rapidly leading to the generation of hydroxyl radical which may in turn initiate membrane lipid peroxidation 2 .…”

“…Metformin and rosuvastatin possibly chelate free iron released from erythrocytes hemolysis under oxidative conditions so decreasing its availability to generate ROS and membrane damage 2,19,20 . In an in-vitro study, Bai et al, 2013 21 , found that metformin can inhibit intracellular ROS generation through inhibiting NADPH oxidase enzyme which is present in high levels in sickle erythrocytes 3 .…”

“…High calcium level may accumulate inside erythrocytes or in extracellular compartment leading to erythrocytes rigidity 26 . Another explanation for the lack of effect of rosuvastatin could be attributed to the use of DMSO as an organic solvent for dissolving rosuvastatin which is poorly soluble in water 19 . DMSO at a concentration ranging from 2-40% can increase intracellular calcium levels by increasing membrane permeability to calcium and may also increase the release of calcium from intracellular pools 27,28 .…”