scholarly journals Tacrine-allyl/propargylcysteine–benzothiazole trihybrids as potential anti-Alzheimer's drug candidates

RSC Advances ◽  
2016 ◽  
Vol 6 (58) ◽  
pp. 53519-53532 ◽  
Author(s):  
Asha Hiremathad ◽  
Karam Chand ◽  
A. Raquel Esteves ◽  
Sandra M. Cardoso ◽  
Rona R. Ramsay ◽  
...  
Keyword(s):  
Mao Inhibition ◽  
Drug Candidates ◽  
Aβ Aggregation

Eight novel trihybrids as potential anti-Alzheimer's drugs showed high AChEI and anti-Aβ aggregation capacity, moderate anti-ROS activity and low MAO inhibition.

Understanding the Binding Mechanism of Amyloid-β Inhibitors from Molecular Simulations

2018 ◽  
Vol 24 (28) ◽  
pp. 3341-3346
Author(s):  
Linh Tran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Specific Binding ◽  
Amyloid Β ◽  
Random Coil ◽  
Binding Mechanism ◽  
Drug Candidates ◽  
Aβ Aggregation ◽  
Potential Inhibitors

In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer’s disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the identification of binding targets has been challenging due to the heterogeneity and metastable nature. A better understanding of Aβ species’ assembly details and structural properties has been more characterized recently. Numerous potential inhibitors have been identified that they can effectively bind to different Aβ species such as monomer, oligomer or protofibril during the inhibition of Aβ aggregation process. This review highlights the diversity of structural ensembles of Aβ species, from monomer to protofibril forms and the specific binding targets by their potential inhibitors. Comprehending the binding mechanism of Aβ inhibitors is indispensable for searching novel drug candidates against early-stage Alzheimer’s disease.

Imidazole: Multi-targeted Therapeutic Leads for the Management of Alzheimer’s Disease

2022 ◽  
Vol 22 ◽  
Author(s):  
Ashwani K. Dhingra ◽  
Bhawna Chopra ◽  
Akash Jain ◽  
Jasmine Chaudhary
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ion ◽  
Acetylcholinesterase Inhibitors ◽  
Drug Candidates ◽  
The Status ◽  
Aβ Aggregation ◽  
Neuro Inflammation ◽  
Therapeutic Leads ◽  
Novel Drug

Background: Alzheimer's disease (AD) is a multifactorial disorder coupled with an array of neuropathological mechanisms, including tau phosphorylation, Aβ aggregation, metal ion deregulation, and oxidative stress, along with neuro-inflammation. The clinically available drugs for the management of AD include four acetylcholinesterase inhibitors and one glutamatergic antagonist. These agents provide only temporary relief from the symptoms by altering the neurotransmitter level in the brain. Objective: Keeping in view the focus on research, the numerous pharmacological activities associated with the aromatic diazole heterocyclic nucleus, imidazole, triggered the medicinal chemist to develop a large number of novel anti-AD compounds targeting multiple pathological mechanisms associated with AD. These prepared analogs represent a higher potential against neurological disorders, including AD. This review article aims an ornately pronounce the therapeutic voyage of imidazole and its analogs as anti-AD. Method: It emphasizes the synthesized imidazole derivatives as anti–AD with multiple targets reviewed from the data available on Pubmed. Result: These compounds diminish the pathophysiological aspects of AD; still, further studies are required to prove the safety and efficacy of these compounds in humans. Conclusion: The review aims to provide knowledge and highlight the status of this moiety in the design and development of novel drug candidates against Alzheimer’s disease conditions. Thus, it paves the way for further work.

Bringing Biocatalysis into the Deuteration Toolbox

2019 ◽  
Author(s):  
Jack Rowbotham ◽  
Oliver Lenz ◽  
Holly Reeve ◽  
Kylie Vincent
Keyword(s):  
Late Stage ◽  
Hydrogen Isotope ◽  
Reductive Amination ◽  
Mechanistic Studies ◽  
Ambient Conditions ◽  
Synthetic Pathway ◽  
Drug Candidates ◽  
Isotopic Selectivity ◽  
Reducing Equivalents

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (<sup>2</sup>H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed <sup>2</sup>H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only <sup>2</sup>H<sub>2</sub>O (D<sub>2</sub>O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed <sup>2</sup>H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from <sup>2</sup>H<sub>2</sub>O solvent to NAD<sup>+</sup>, with H<sub>2</sub> gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

Recent Advances in Obesity: The Role of Turmeric Tuber and Its Metabolites in the Prophylaxis and Therapeutical Strategies

2019 ◽  
Vol 25 (37) ◽  
pp. 4837-4853 ◽  
Author(s):  
Agata Jarząb ◽  
Wirginia Kukula-Koch
Keyword(s):  
Body Weight ◽  
21St Century ◽  
The Body ◽  
Excess Body Weight ◽  
Inflammatory Reactions ◽  
Drug Candidates ◽  
Scientific Papers ◽  
Important Health ◽  
High Concern

Background: Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern. Objective: This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber – a commonly used spice - as an anti-obesity agent. Methods: Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants’ regulatory properties in obesity was summarized. Particular attention was paid to curcumin – the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed. Results: Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties. Conclusions: This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Antitubercular Marine Natural Products

2018 ◽  
Vol 25 (20) ◽  
pp. 2304-2328 ◽  
Author(s):  
Lishu Wang ◽  
Jungfeng Wang ◽  
Juan Liu ◽  
Yonghong Liu
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Antitubercular Activity ◽  
Marine Resources ◽  
Drug Candidates ◽  
New Drug ◽  
Chemical Constitution

Due to the importance of nature as a source of new drug candidates, the purpose of this article is to emphasize the marine natural products, which exhibit antitubercular activity, published between January 2000 and May 2016, with 138 quotations to 250 compounds obtained from marine resources. These metabolites are organized by chemical constitution and named as simple alkyl lipids derivatives, aromatics derivatives, peptides, alkaloids, terpenoids, steroids, macrolides, and polycyclic polyketides.

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

2018 ◽  
Vol 25 (5) ◽  
pp. 636-658 ◽  
Author(s):  
Jan Pokorny ◽  
Lucie Borkova ◽  
Milan Urban
Keyword(s):  
Biological Activities ◽  
Synthetic Approach ◽  
Clinical Use ◽  
New Approach ◽  
Click Reactions ◽  
Drug Candidates ◽  
The Past ◽  
Low Toxicity ◽  
New Compounds ◽  
Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

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