Topics

Isoquinoline alkaloids from the roots of Zanthoxylum rigidum as multi-target inhibitors of cholinesterase, monoamine oxidase A and Aβ aggregation.

07:00 EST 4th March 2020 | BioPortfolio

Summary of "Isoquinoline alkaloids from the roots of Zanthoxylum rigidum as multi-target inhibitors of cholinesterase, monoamine oxidase A and Aβ aggregation."

Multifactorial neurodegenerative disorders such as Alzheimer's disease (AD) are considered a growing public health problem due the rising incidence and low effectiveness of current treatments [6]. Since pharmacotherapy based on a single target has been insufficient for drug development in complex diseases, the emerging multi-target approach is a promising strategy for the search of new anti-AD drug candidates. Herein described natural isoquinoline alkaloids were investigated for multi-target activity on key mechanisms associated with the AD's pathogenesis, i.e. cholinergic depletion, beta amyloid (Aβ) aggregation and oxidative stress. Alkaloid isolation from root extract of Zanthoxylum rigidum was carried out using multi-step chromatography and TLC-bioautography against acetylcholinesterase (AChE) giving eight purified isoquinoline alkaloids. Isolated compounds were tested for inhibitory activity against cholinesterase (AChE and BChE), monoamine oxidase (MAO-A and B) and Aβ aggregation. Our study revealed two benzophenanthridine alkaloids, nitidine (5) and avicine (7), as the most potent multi-target candidates. Both showed dual cholinesterase inhibition, being more active against AChE over BChE, with IC values in sub-micromolar range in AChE. Kinetic analysis with cholinesterase showed, that both compounds are reversible-mixed inhibitors, where avicine (7) presented highest potency with K values of 0.063 µM (EeAChE), 0.511 µM (HrAChE) and 0.123 µM (EqBChE). In addition, these alkaloids presented moderate Aβ anti-aggregation activity and MAO-A inhibition with IC values between 0.5 and 2 µM. Our findings suggest that avicine (7) is a promising natural compound and multifunctional candidate representing a suitable starting point for the development of new therapeutic agents for Alzheimer's disease.

Affiliation

Journal Details

This article was published in the following journal.

Name: Bioorganic chemistry
ISSN: 1090-2120
Pages: 103722

Links

DeepDyve research library

PubMed Articles [9387 Associated PubMed Articles listed on BioPortfolio]

Metabolomic profiling of Zanthoxylum species: Identification of anti-cholinesterase alkaloids candidates.

The isolation of bioactive compounds from natural sources is a key step in drug discovery and development, however, this procedure is usually expensive and difficult due to the complexity and the limi...

Enantioselective Divergent Syntheses of (+)-Bulleyanaline and Related Isoquinoline Alkaloids from the Genus Corydalis.

The isoquinoline alkaloids isolated from the genus Corydalis possess potent and diverse biological activities. Herein, a concise, divergent, and enantioselective route to access these natural products...

Alkaloids from the stem barks of Erythrina stricta.

Four previously undescribed erythrinan alkaloids, 8α-acetonylerythristemine, 8α-acetonylerysotrine, 10β-hydroxy-11β-methoxyerysotramidine and 3-epierysotrine, one undescribed pyrrolidine derivativ...

Bioactive bisbenzylisoquinoline alkaloids from the roots of Stephania tetrandra.

Ten new bisbenzylisoquinoline alkaloids (1-10) and eight known analogues (11-18) were obtained from the roots of Stephania tetrandra. The structures of these compounds were determined by spectroscopic...

Natural protoberberine alkaloids, identified as potent selective LSD1 inhibitors, induce AML cell differentiation.

Natural protoberberine alkaloids were first identified and characterized as potent, selective and cellular active lysine specific demethylase 1 (LSD1) inhibitors. Due to our study, isoquinoline-based ...

Clinical Trials [5407 Associated Clinical Trials listed on BioPortfolio]

Effect of Zanthoxylum Nitidum Tincture for Paronychia Caused by Afatinib

This is a randomized control trial evaluating the efficacy of zanthoxylum nitidum tincture on preventing progression of paronychia caused by afatinib from grade 1 to grade 2/3. Enrolled pa...

The Effect of Oral Zanthoxylum Schinifolium Seed Oil in Individuals With Dry Eye Disease

The purpose of this study is to evaluate the clinical efficacy and safety of 10-weeks oral consumption of Zanthoxylum schinifolium seed Oil (ZSO) in patients with mild dry eye disease.

Assessing Goldenseal-drug Interactions Using a Probe Drug Cocktail Approach

Goldenseal is a botanical natural product commonly used to self-treat symptoms of the common cold and many digestive disorders. Goldenseal products typically contain the isoquinoline alkal...

Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer

In metastatic breast cancer (MBC) patients who have already received anthracyclines, taxanes, antimetabolites and vinca-alkaloids and have developed drug resistance to these drugs, therape...

Long-Term Study of Multi-target Therapy as Continuous Induction and Maintenance Treatment for Lupus Nephritis

An multi-site, randomized, prospective study to compare the efficacy and safety of multi-target therapy as continuous induction and maintenance treatment versus CTX- Aza therapy.

Medical and Biotech [MESH] Definitions

A plant genus of the family RUTACEAE. Most plants that are called Fagara are actually Zanthoxylum. Some members of Zanthoxylum are reclassified from ELEUTHEROCOCCUS, Melicope, and EVODIA. The twigs are used as dental brushing sticks (TOOTHBRUSHING).

A plant genus of the family PAPAVERACEAE that contains isoquinoline alkaloids.

A plant genus of the family FUMARIACEAE that contains fumariline and other isoquinoline alkaloids.

A plant genus of the family RANUNCULACEAE. Members contain isoquinoline alkaloids.

A plant genus of the family RANUNCULACEAE. Members contain BERBERINE and other isoquinoline ALKALOIDS.

Quick Search


DeepDyve research library

Relevant Topics

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...

Public Health
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...


Searches Linking to this Article