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Targeted Delivery of Cytotoxic Metal Complexes into Cancer Cells with and without Macromolecular Vehicles

Electronic Theses of Indian Institute of Science

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Field Value
 
Title Targeted Delivery of Cytotoxic Metal Complexes into Cancer Cells with and without Macromolecular Vehicles
 
Creator Mitra, Raja
 
Subject Metal Complexes - Cancer Therapy
Targeted Drug Delivery
Metallodrugs
Chemotherapy
Anticancer Active Metal Complexes
Cytotoxic Metal Complexes - Targeted Drug Delivery - Cancer Cells
Anticancer Hydrogen Bond-Ruthenium Complexes
Anticancer Half-Sandwich Ruthenium Complexes
Anticancer Metallodrugs
Cancer - Treatment
Targeted Therapy
Ru(II)-Heterocycle Complexes
Ru(II) Complexes
Cytotoxic Copper Complexes
Medicinal Chemistry
 
Description Anticancer active metal complexes such as cisplatin are routinely used for treating various cancers since 1978. However, the side effects of cisplatin overwhelm its therapeutic potential, especially in the latter stages of treatment. The nonspecific cytotoxicity of drugs could be avoided if targeted delivery to cancer cells is achieved using two different methodologies namely, enhanced permeability and retention in solid tumors (EPR) and receptor mediated endocytosis using a homing agent (RME). Ru(II)-arene complexes which are delivered specifically into cancer cells by the transferrin enzyme are less toxic compared to other metal complexes. The thesis describes the synthesis and use of Ru(II)-η6cymene complexes with different ancillary ligands which modulates the anticancer activity and the utility of two macromolecular vehicles in directed drug delivery.
Ru(II)-η6cymene complexes with different heterocyclic ancillary ligands are synthesized and their anticancer activity tested against various cancer cell lines. Ruthenium complexes with mercaptobenzothiazoles are found to be quite active against the H460 cell lines that overexpress transferrin receptors and non-cytotoxic to the normal cell line, HEL299. Biophysical studies show that complexes (H1 and H8) can unwind the pBR322 DNA and inhibit the Topo IIα enzyme. A unique biphasic melting curve of CT DNA is observed in the presence of H1 which is attributed to formation of a dinuclear species (H20).
Half-sandwich complexes of 6-thioguanine (6-TG) have also been prepared to improve the delivery and efficacy of 6-TG which is used in spite of a deleterious photoreaction. The Ru complexes cytotoxic to several leukemia cell lines. As they are photostable and anticancer active, they are better than 6-TG. Anticancer activity exhibiting piazselenols are used as ancillary ligands to make Ru(II)-arene complexes. Unfortunately, 1H NMR spectra suggests that piazselenol complexes dissociate in solution. However, the nitro substituted piazselenol and its Ru complex show the greatest cytotoxicity (
 
Contributor Samuelson, A G
 
Date 2018-04-12T09:37:58Z
2018-04-12T09:37:58Z
2018-04-12
2013
 
Type Thesis
 
Identifier http://etd.iisc.ernet.in/2005/3392
http://etd.iisc.ernet.in/abstracts/4258/G25854-Abs.pdf
 
Language en_US
 
Relation G25854