Synthesis and Inhibitory Activity of Atorvastatin Conjugate with a Branched Asialoglycoprotein Receptor Ligand Containing Three N-Acetyl-d-galactosamine Residues
Svetlana Yu. Maklakova, Maria P. Mazhuga, Anton V. Lopukhov, Karina R. Gibadullina, Natalia L. Klyachko, Alexander G. Majouga, Elena Kimovna Beloglazkina · Russian Journal of Organic Chemistry · 2023
Abstract A novel atorvastatin conjugate was synthesized by a multistep procedure, using a branched N-acetylgalactosamine ligand for asialoglycoprotein receptor targeting. The molar solubility of the synthesized conjugate was 6.1 ± 0.9 mM, which is almost 60 times higher compared to unmodified atorvastatin. The hydrolysis products of the conjugate demonstrated effective inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.