Novel Arylalkenylpropargylamines as Neuroprotective, Potent, and Selective Monoamine Oxidase B Inhibitors for the Treatment of Parkinson’s Disease

Huleatt, Paul B.; Khoo, Mui Ling; Chua, Yi Yuan; Tan, Tiong Wei; Liew, Rou Shen; Balogh, Balázs; Deme, Ruth; Gölöncsér, Flóra; Magyar, K.; Sheela, David P.; Ho, Han Kiat; Sperlágh, Beáta; Mátyus, Péter; Chai, Christina L. L.

doi:10.1021/jm501722s

Cited by 45 publications

(30 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interest in expanding this research to clinical translational applications is based upon concerns that long‐term treatment of PD with levodopa often leads to end‐of‐dose and/or tachyphylactic exacerbation of signs and symptoms, and can evoke significant side effects, such as dyskinesia (Shulman, Taback, Bean, & Weiner, ). These deleterious effects have prompted the search for agents that might be useful in the prevention and treatment of PD, inclusive of other pharmacological approaches (Carradori & Silvestri, ; Huleatt et al, ), the use of low dose radiation (El‐Ghazaly, Sadik, Rashed, & Abd‐El‐Fattah, ; Kojima et al,) and herbal extracts, many of which are constituents of traditional Asian pharmacopeia (Zhang et al, ). Several candidate agents have been screened using in vitro models (e.g., PC‐12, SH‐SY5Y, and MN9 cells) that mimic key features of PD when exposed to agents such as 6‐OHDA, MPTP, rotenone, and paraquat.…”

Section: Hormesis and Parkinson's Diseasementioning

confidence: 99%

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

Calabrese

Santoro

Salinaro

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

Age-related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical signaling occurring from the intracellular to the network-systemic level throughout the brain. A number of agents that affect the onset and progression of Parkinson's disease (PD)-like effects in experimental models exhibit temporal features, and mechanisms of hormetic dose responses. These findings have particular significance since the hormetic dose response describes the amplitude and range of potential therapeutic effects, thereby affecting the design and conduct of studies of interventions against PD (and other neurodegenerative diseases), and may also be important to a broader consideration of hormetic processes in resilient adaptive responses that might afford protection against the onset and/or progression of PD and related disorders.

show abstract

Section: Hormesis and Parkinson's Diseasementioning

confidence: 99%

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

Calabrese

Santoro

Salinaro

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…This would also result in a reduced Lewis‐acidity. The loaded HF can further be transferred to alkynes by hydrofluorination under mild conditions to yield fluorinated alkenes, which are currently of interest as fluorinated building blocks …”

Section: Discussionmentioning

confidence: 99%

A HF Loaded Lewis‐Acidic Aluminium Chlorofluoride for Hydrofluorination Reactions

Kervarec

Kemnitz

Scholz

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…To develop novel neuroprotective agents, Huleatt et al 205 increase which is much greater than RSG (which shows only 6% increase) on rotenone treatment of PC12 cells.…”

Section: Propargylaminesmentioning

confidence: 99%

“…To develop novel neuroprotective agents, Huleatt et al synthesized a library of novel arylalkenylpropargylamines ( 144‐177 ) and tested them for inhibitory activities against MAOs (Figure ). A number of highly potent and selective MAO‐BIs were identified.…”

Section: Discovery and Development Of Mao‐b Inhibitors (2015‐2018)mentioning

confidence: 99%

See 1 more Smart Citation

Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update

Tripathi

Ayyannan

2019

Medicinal Research Reviews

View full text Add to dashboard Cite

Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. This review summarizes our current understanding on MAO‐A/MAO‐B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAO‐B as a potential therapeutic target for the development of medications treating neurodegenerative disorders. It also highlights the recent developments in the discovery of potential MAO‐B inhibitors (MAO‐BIs) belonging to diverse chemical scaffolds, arising from intensive chemical‐mechanistic and computational studies documented during past 3 years (2015‐2018), with emphases on their potency and selectivity. Importantly, readers will gain knowledge of various newly established MAO‐BI scaffolds and their development potentials. The comprehensive information provided herein will hopefully accelerate ideas for designing novel selective MAO‐BIs with superior activity profiles and critical discussions will inflict more caution in the decision‐making process in the MAOIs discovery.

show abstract

Novel Arylalkenylpropargylamines as Neuroprotective, Potent, and Selective Monoamine Oxidase B Inhibitors for the Treatment of Parkinson’s Disease

Cited by 45 publications

References 33 publications

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

A HF Loaded Lewis‐Acidic Aluminium Chlorofluoride for Hydrofluorination Reactions

Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update

Contact Info

Product

Resources

About