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.

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 (IC50 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.

• Authors: Jing Ma, Qingpeng Wang, Zhonglv Huang, Xiande Yang, Quandeng Nie, Wenpei Hao, Peng George Wang, Xin Wang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 60 Issue 13 Pg. 5736-5748 (07 13 2017) ISSN: 1520-4804 [Electronic] United States
• PMID: 28603992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Glucose Transport Proteins, Facilitative
• Organic Cation Transport Proteins
• Organoplatinum Compounds
• Prodrugs
• Serum Albumin

Topics

• Antineoplastic Agents (administration & dosage, chemistry, metabolism, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Delivery Systems
• Glucose Transport Proteins, Facilitative (metabolism)
• Glycosylation
• Humans
• Molecular Docking Simulation
• Neoplasms (drug therapy, metabolism)
• Organic Cation Transport Proteins (metabolism)
• Organoplatinum Compounds (administration & dosage, chemistry, metabolism, pharmacology)
• Prodrugs (administration & dosage, chemistry, metabolism, pharmacology)
• Serum Albumin (metabolism)