Non-traditional platinum compounds for improved cellular accumulation and tumor targeting

Chapter 1. Introduction to Non-Traditional Platinum Compounds for Improved Uptake, Oral Bioavailability, and Tumor Targeting The path to more potent platinum anticancer drugs with fewer side effects lies in the exploration of non-traditional platinum compounds, which do not necessarily contain the canonical ligand set of two labile leaving groups and two am(m)ine ligands. Cationic, platinum(IV), and multinuclear complexes are considered. Advances in tumor targeting using platinum complexes are also discussed. Chapter 2. Structure-Activity Relationship for the Uptake of Platinum(ll) Compounds by Human Organic Cation Transporters Although the platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin form similar adducts on DNA, only oxaliplatin is active in colorectal cancer. Human organic cation transporters hOCT1 and hOCT2 markedly increase oxaliplatin, but not cisplatin or carboplatin, accumulation and potency in cells. These transporters are also present in human colorectal cancers and are likely to play an important role in the efficacy of oxaliplatin. Chapter 3. Synthesis of Pt(llI) and Pt(IV) Compounds for Uptake by the Organic Cation Transporters: Extension of Structure-Activity Relationships A structure-activity relationship for the cellular accumulation of platinum compounds due to the organic cation transporters was developed and extended to design cationic compounds as particularly potent colorectal cancer drugs.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Lovejoy, Katherine Summer, 1981-

Advisor dc:contributor.advisor

• Stephen J. Lippard.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/55091

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/55091