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Glycosylated Platinum(IV) Complexes as Substrates for Glucose Transporters (GLUTs) and Organic Cation Transporters (OCTs) Exhibited Cancer Targeting and Human Serum Albumin Binding Properties for Drug Delivery.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2017 Jul 13; Vol. 60 (13), pp. 5736-5748. Date of Electronic Publication: 2017 Jun 27. - Publication Year :
- 2017
-
Abstract
- Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo. Galactoside Pt(IV), glucoside Pt(IV), and mannoside Pt(IV) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(IV) complexes 5, 6, 7, and 8 (IC <subscript>50</subscript> 0.24-3.97 μM) had better antitumor activity of nearly 166-fold higher than the positive controls cisplatin (1a), oxaliplatin (3a), and satraplatin (5a). The presence of a hexadecanoic chain allowed binding with human serum albumin (HSA) for drug delivery, which not only enhanced the stability of the inert platinum(IV) prodrugs but also decreased their reduction by reductants present in human whole blood. Their preferential accumulation in cancer cells compared to noncancerous cells (293T and 3T3 cells) suggested that they were potentially safe for clinical therapeutic use.
- Subjects :
- Antineoplastic Agents administration & dosage
Antineoplastic Agents metabolism
Cell Line, Tumor
Cell Survival drug effects
Drug Delivery Systems
Glycosylation
Humans
Molecular Docking Simulation
Neoplasms drug therapy
Neoplasms metabolism
Organoplatinum Compounds administration & dosage
Organoplatinum Compounds metabolism
Prodrugs administration & dosage
Prodrugs chemistry
Prodrugs metabolism
Prodrugs pharmacology
Serum Albumin metabolism
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Glucose Transport Proteins, Facilitative metabolism
Organic Cation Transport Proteins metabolism
Organoplatinum Compounds chemistry
Organoplatinum Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 60
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28603992
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.7b00433