ChemInform Abstract: Synthesis and Pharmacological Activities of a Novel Tripeptide Mimetic Dopamine Prodrug.

Wang, H.‐P.; Lee, J.‐S.; Tsai, Ming-Cheng; Lu, H.H.; Hsu, Wu‐Huei

doi:10.1002/chin.199606218

Cited by 5 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although L-dopa enters CNS via the large neutral amino acid transporters at BBB and is enzymatically cleaved in the brain to release dopamine, a large percentage of circulating L-dopa does not penetrate the BBB and, as a consequence, undergoes peripheral decarboxylation to generate metabolites that cause dopamine-related side effects. 8 While this study was in progress, glycoconjugates of dopamine and L-dopa were explored by Bonina and De Caprariis 9 as a means to increase their BBB permeability by carrier-mediated transport (GLUT 1). Several peptidyl prodrugs of dopamine and L-dopa have also been shown to increase the BBB permeability of L-dopa along with improved bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Glutathione Peptidomimetics as Components of Anti-Parkinson Prodrugs

Vince

2008

J. Med. Chem.

View full text Add to dashboard Cite

Plethoras of CNS-active drugs fail to effect their pharmacologic response due to their in vivo inability to cross the blood-brain barrier (BBB). The classical prodrug approach to overcome this frailty involves lipophilic derivatives of the polar drug, but we herein report a novel approach by which endogenous transporters at BBB are exploited for brain drug delivery. The crucial role played by glutathione in pathogenesis of Parkinson's and the presence of its influx transporters at the basolateral membrane of BBB served as the basis for our anti-Parkinson prodrug design strategy. A metabolically stable analogue of glutathione is used as a carrier for delivery of dopamine and adamantamine. An account of successful syntheses of these prodrugs along with their transport characteristics and stability determination is discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Glutathione Peptidomimetics as Components of Anti-Parkinson Prodrugs

Vince

2008

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…Wang and co-workers developed a tripeptide mimetic prodrug of 138 ( 141 , Figure 58 ) as a delivery system for improving oral absorption, in which d - p -hydroxyphenylglycine- l -proline was attached to 140 [ 187 ].…”

Section: Drugs and Diseasesmentioning

confidence: 99%

“…The tripeptide was well absorbed during a perfusion study in rat intestine, devoid of side effect of 138 on isolated muscles and significantly decreased the methamphetamine-induced rotational behavior in nigrostriatal-lesioned rats, suggesting that it might be an effective agent for Parkinson’s disease [ 187 ]. In order to enhance the brain uptake of cationic dopamine, Peura et al synthesized three amino acid prodrugs of 138 ( 142a – c , Figure 59 ) and evaluated their physicochemical properties, as well as (i) their LAT1-binding and BBB permeation; (ii) brain uptake after IV administration and releasing of 138 ability in rat brain after intraperitoneal administration [ 188 ].…”

Section: Drugs and Diseasesmentioning

confidence: 99%

Amino Acids in the Development of Prodrugs

Vale

Ferreira

Matos³

et al. 2018

Molecules

View full text Add to dashboard Cite

Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.

show abstract

“…Several LD peptides (54, 59, 61, 64, 69, 70, and 73) showed central activity comparable to LD, to cause a lower degree of stereotypic behavior, and to be relatively non-toxic in mice. Afterwards a tripeptide mimetic LD prodrug, in which D-p-hydroxyphenylglycine L-proline is attached to LD (74), was synthesized as a delivery system for improving LD oral absorption [45].…”

Section: Peptidyl Prodrugs Of Ldmentioning

confidence: 99%

L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment

Stefano

Sozio²,

Cerasa³

et al. 2011

CPD

View full text Add to dashboard Cite

L-Dopa is the mainstay of Parkinson's disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation. Starting from these considerations the prodrug approach has been applied to L-Dopa in order to overcome its metabolism problems and to improve its bioavailability. The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the formation of the desired derivative.

show abstract

ChemInform Abstract: Synthesis and Pharmacological Activities of a Novel Tripeptide Mimetic Dopamine Prodrug.

Cited by 5 publications

References 1 publication

Design, Synthesis and Biological Evaluation of Glutathione Peptidomimetics as Components of Anti-Parkinson Prodrugs

Design, Synthesis and Biological Evaluation of Glutathione Peptidomimetics as Components of Anti-Parkinson Prodrugs

Amino Acids in the Development of Prodrugs

L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment

Contact Info

Product

Resources

About