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Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Feb 01; Vol. 28 (3), pp. 382-387. Date of Electronic Publication: 2017 Dec 14. - Publication Year :
- 2018
-
Abstract
- Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug - paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents, Phytogenic chemical synthesis
Antineoplastic Agents, Phytogenic chemistry
Asialoglycoprotein Receptor metabolism
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Delivery Systems
Drug Screening Assays, Antitumor
Galactose analogs & derivatives
Galactose chemistry
Hep G2 Cells
Humans
Liver Neoplasms metabolism
Liver Neoplasms pathology
Molecular Structure
Paclitaxel chemical synthesis
Paclitaxel chemistry
Small Molecule Libraries chemical synthesis
Small Molecule Libraries chemistry
Structure-Activity Relationship
Antineoplastic Agents, Phytogenic pharmacology
Asialoglycoprotein Receptor antagonists & inhibitors
Carcinoma, Hepatocellular drug therapy
Galactose pharmacology
Liver Neoplasms drug therapy
Paclitaxel pharmacology
Small Molecule Libraries pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 29269214
- Full Text :
- https://doi.org/10.1016/j.bmcl.2017.12.032