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Improving blood brain barrier permea...

Desino, Kelly E.

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Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects./
Author:	Desino, Kelly E.
Description:	171 p.
Notes:	Adviser: Kenneth L. Audus.
Contained By:	Dissertation Abstracts International69-03B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3297991
ISBN:	9780549498636

Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects.
Desino, Kelly E.

Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects. - 171 p.

Adviser: Kenneth L. Audus.

Thesis (Ph.D.)--University of Kansas, 2008.

The blood brain barrier is the body's natural defense system for limiting the brain's exposure to potentially harmful xenobiotics. This barrier exists between the blood of the systemic circulation and the brain and is made up of brain endothelial cells which have tight junctions, reduced pinocytosis, minimal fenestration and increased expression of metabolizing enzymes and membrane transporters capable of efflux. Estimates predict that the blood brain barrier may be capable of limiting up to 98% of all drugs from entering the brain and is therefore a major obstacle in drug delivery. The research presented herein highlights several small molecules that possess chemotherapeutic and neuroprotective properties. These molecules also represent various strategies for improving blood brain barrier penetration. Derivatives of the microtubule stabilizing agent paclitaxel were investigated in which chemical modification was employed to reduce interaction with the efflux transporter P-glycoprotein, which is critical in limiting paclitaxel's entry into the brain. TH-237A, another microtubule stabilizing agent that is structurally very different from paclitaxel was also characterized and was shown to have excellent blood brain barrier penetration. Additionally, derivatives of the monoamine oxidase inhibitor tranylcypromine were explored that have fatty acid and lipoamino acid chains of varying length attached to improve blood brain barrier permeability. In order for these compounds to exert their mechanism of action as either chemotherapeutic or neuroprotective agents, they must be able to penetrate the blood brain barrier. The specific objective of this project was to explore various chemical approaches to improving blood brain barrier permeability using pharmacologically relevant molecules.

ISBN: 9780549498636Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects.
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020 $a 9780549498636
035 $a (UMI)AAI3297991
035 $a AAI3297991
040 $a UMI $c UMI
100 1 $a Desino, Kelly E. $3 1265019
245 1 0 $a Improving blood brain barrier permeation of small molecules exhibiting chemotherapeutic and neuroprotective effects.
300 $a 171 p.
500 $a Adviser: Kenneth L. Audus.
500 $a Source: Dissertation Abstracts International, Volume: 69-03, Section: B, page: 1664.
502 $a Thesis (Ph.D.)--University of Kansas, 2008.
520 $a The blood brain barrier is the body's natural defense system for limiting the brain's exposure to potentially harmful xenobiotics. This barrier exists between the blood of the systemic circulation and the brain and is made up of brain endothelial cells which have tight junctions, reduced pinocytosis, minimal fenestration and increased expression of metabolizing enzymes and membrane transporters capable of efflux. Estimates predict that the blood brain barrier may be capable of limiting up to 98% of all drugs from entering the brain and is therefore a major obstacle in drug delivery. The research presented herein highlights several small molecules that possess chemotherapeutic and neuroprotective properties. These molecules also represent various strategies for improving blood brain barrier penetration. Derivatives of the microtubule stabilizing agent paclitaxel were investigated in which chemical modification was employed to reduce interaction with the efflux transporter P-glycoprotein, which is critical in limiting paclitaxel's entry into the brain. TH-237A, another microtubule stabilizing agent that is structurally very different from paclitaxel was also characterized and was shown to have excellent blood brain barrier penetration. Additionally, derivatives of the monoamine oxidase inhibitor tranylcypromine were explored that have fatty acid and lipoamino acid chains of varying length attached to improve blood brain barrier permeability. In order for these compounds to exert their mechanism of action as either chemotherapeutic or neuroprotective agents, they must be able to penetrate the blood brain barrier. The specific objective of this project was to explore various chemical approaches to improving blood brain barrier permeability using pharmacologically relevant molecules.
590 $a School code: 0099.
650 4 $a Chemistry, Pharmaceutical. $3 550957
690 $a 0491
710 2 $a University of Kansas. $b Pharmaceutical Chemistry. $3 1265020
773 0 $t Dissertation Abstracts International $g 69-03B.
790 $a 0099
790 1 0 $a Audus, Kenneth L., $e advisor
790 1 0 $a Borchardt, Ronald T. $e committee member
790 1 0 $a Lunte, Susan $e committee member
790 1 0 $a Michaelis, Mary Lou $e committee member
790 1 0 $a Siahaan, Teruna $e committee member
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3297991