158955-67-0Relevant academic research and scientific papers
The design and evaluation of an l-dopa–lazabemide prodrug for the treatment of Parkinson’s disease
Hoon, Monique,Petzer, Jacobus P,Viljoen, Francois,Petzer, Anél
, (2017)
L-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the symptomatic relief of the advanced stages of Parkinson’s disease. The oral bioavailability of L-dopa, however, is only about 10% to 30%, and less than 1% of the oral dose is estimated to reach the brain unchanged. L-Dopa’s physicochemical properties are responsible for its poor bioavailability, short half-life and the wide range of inter- and intrapatient variations of plasma levels. An L-dopa–lazabemide prodrug is proposed to overcome the problems associated with L-dopa absorption. Lazabemide is a monoamine oxidase (MAO)-B inhibitor, a class of compounds that slows the depletion of dopamine stores in Parkinson’s disease and elevates dopamine levels produced by exogenously administered L-dopa. L-Dopa was linked at the carboxylate with the primary aminyl functional group of lazabemide via an amide, a strategy which is anticipated to protect L-dopa against peripheral decarboxylation and possibly also enhance the membrane permeability of the prodrug. Selected physicochemical and biochemical properties of the prodrug were determined and included lipophilicity (logD), solubility, passive diffusion permeability, pKa, chemical and metabolic stability as well as cytotoxicity. Although oral and i.p. treatment of mice with the prodrug did not result in enhanced striatal dopamine levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly depressed compared to saline, L-dopa and carbidopa/L-dopa treatment. Based on the results, further preclinical evaluation of the L-dopa–lazabemide prodrug should be undertaken with the aim of discovering prodrugs that may be advanced to the clinical stages of development.
COMPOSITIONS AND METHODS FOR SINGLE-STEP MULTIPURPOSE SURFACE FUNCTIONALIZATION
-
Page/Page column 40; 41, (2021/07/02)
Compositions and methods for functionalizing a variety of surfaces are provided herein. The compositions include compounds of formula (I), which react with azido compounds (R-N3) to form cycloadducts that can spontaneously polymerize on a surfa
Delivery of a system xc?inhibitor by a redox-responsive levodopa prodrug nanoassembly for combination ferrotherapy
Chen, Yuan,Huang, Yong,Li, Bowen,Ping, Yuan,Tang, Honglin,Xia, Hongguang,Xin, Huhu,Zhang, Fu
, p. 7172 - 7181 (2021/09/22)
A comprehensive understanding of ferroptosis signaling pathways significantly contributes to the advances in cancer ferrotherapy. Herein, we constructed a self-assembled prodrug nanosystem targeting system xc?, a key regulator for ferroptosis, to amplify the therapeutic efficacy of cancer ferrotherapy. The prodrug nanosystem is assembled between sulfasalazine (SSZ, a ferroptosis resistance inhibitor) and disulfide-bridged levodopa (DSSD) that can chelate Fe2+ions to form SSZ-Fe2+@DSSD, and the resulting nanoassembly can not only inhibit ferroptosis resistance, but also generate ROS in the tumor microenvironment. Whereas the prodrug nanosystem is stable in the physiological environment, it becomes unstable in the tumoral and intracellular reductive microenvironment, where the disulfide linkers are disrupted by high levels of glutathione (GSH), triggering the release of active Fe2+and SSZ. Under the Fenton reaction, the released Fe2+thus can induce ferroptosis, which is amplified by SSZ-mediated inhibition of ferroptosis resistance to synergistically improve the therapeutic efficacy of ferroptosis. Our study thus provides an innovative prodrug strategy to advance anticancer ferroptosis.
PANTETHEINE DERIVATIVES AND USES THEREOF
-
, (2020/06/19)
The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
Targeted double-stimulation responsiveness multifunction cerium dioxide nano-medicine carrying system capable of degrading polydopamine packs
-
Paragraph 0042; 0043; 0044, (2018/03/25)
The invention relates to a targeted double-stimulation responsiveness multifunction cerium dioxide nano-medicine carrying system capable of degrading polydopamine packs. According to the system, cerium dioxide with cytotoxicity serves as a medicine carryi
Water-soluble L-DOPA esters
-
Paragraph 0090, (2018/05/24)
The present invention relates to novel compounds of the formula I, methods for their preparation and their use for treatment of diseases. The invention discloses the synthesis of levodopa (L-DOPA) esters by coupling polyhydroxy compounds or their derivatives to the L-DOPA carboxyl group. The synthesis allows to produce L-DOPA derivatives which are highly soluble in water as well as aqueous and biocompatible liquids and have an improved hydrolytic stability in water or aqueous and biocompatible media for an application over several days. The invention helps producing L-DOPA substances for applications in the fields of medicine, biology and medical engineering as well as in the pharmaceutical industry.
ESSENTIAL FATTY ACID COMPOUNDS
-
Page/Page column 13-14, (2010/10/03)
The invention provides compounds which include L-DOPA or dopamine linked to an essential fatty acids. The general formula is set out below: R1-Z-O-(CH2)n-CH(R3)-(CH2)mO-Y-R2. Rs
A New Convenient Route for the Synthesis of DOPA Peptides
Nakonieczna, Lucja,Przychodzen, Witold,Chimiak, Andrzej
, p. 1055 - 1058 (2007/10/02)
The tert-butyldimethylsilyl group as the catechol protective group of DOPA (compound 1a), Boc-DOPA (compound 1b) and DOPA esters (compounds 2a-c) is introduced.The compounds 2a-c and 1b are used as the starting substrates for the synthesis of the protecte
