Publications by authors named "Johant Lakey-Beitia"

13 Publications

  • Page 1 of 1

β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19.

Hum Vaccin Immunother 2021 Mar 2:1-6. Epub 2021 Mar 2.

The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India.

Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial.
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http://dx.doi.org/10.1080/21645515.2021.1880210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938654PMC
March 2021

Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids.

Comb Chem High Throughput Screen 2021 Feb 28. Epub 2021 Feb 28.

Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103. Panama.

Background: Red mamey fruit known as P. sapota, comes from trees found in Mesoamerica and Asia. This fruit is considered a nutraceutical food due to it's a food and has multiple beneficial health including anti-amyloidogenic activity and potential anti-tumorigenic property. Red mamey fruit contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the β-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proved to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes.

Objective: Summarize the chemistry and biological activity of the studied carotenoids present in this fruit until now.

Method: An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoid and its purity. Atmospheric pressure chemical ionization is used to determine the molecular weight of carotenoid. Nuclear magnetic resonance is used to determine the structure of carotenoids.

Result: For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization.

Conclusion: it is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.
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http://dx.doi.org/10.2174/1386207324666210301093711DOI Listing
February 2021

Computational Evaluation of Interaction Between Curcumin Derivatives and Amyloid-β Monomers and Fibrils: Relevance to Alzheimer's Disease.

J Alzheimers Dis 2020 Dec 16. Epub 2020 Dec 16.

Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, Panama.

Background: The most important hallmark in the neuropathology of Alzheimer's disease (AD) is the formation of amyloid-β (Aβ) fibrils due to the misfolding/aggregation of the Aβ peptide. Preventing or reverting the aggregation process has been an active area of research. Naturally occurring products are a potential source of molecules that may be able to inhibit Aβ42 peptide aggregation. Recently, we and others reported the anti-aggregating properties of curcumin and some of its derivatives in vitro, presenting an important therapeutic avenue by enhancing these properties.

Objective: To computationally assess the interaction between Aβ peptide and a set of curcumin derivatives previously explored in experimental assays.

Methods: The interactions of ten ligands with Aβ monomers were studied by combining molecular dynamics and molecular docking simulations. We present the in-silico evaluation of the interaction between these derivatives and the Aβ42 peptide, both in the monomeric and fibril forms.

Results: The results show that a single substitution in curcumin could significantly enhance the interaction between the derivatives and the Aβ42 monomers when compared to a double substitution. In addition, the molecular docking simulations showed that the interaction between the curcumin derivatives and the Aβ42 monomers occur in a region critical for peptide aggregation.

Conclusion: Results showed that a single substitution in curcumin improved the interaction of the ligands with the Aβ monomer more so than a double substitution. Our molecular docking studies thus provide important insights for further developing/validating novel curcumin-derived molecules with high therapeutic potential for AD.
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http://dx.doi.org/10.3233/JAD-200941DOI Listing
December 2020

Polyphenols as Potential Metal Chelation Compounds Against Alzheimer's Disease.

J Alzheimers Dis 2020 Jun 15. Epub 2020 Jun 15.

Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, Panama.

Alzheimer's disease (AD) is the most common neurodegenerative disease affecting more than 50 million people worldwide. The pathology of this multi factorial disease is primarily characterized by the formation of amyloid-β (Aβ) aggregates; however, other etiological factors including metal dyshomeostasis, specifically copper (Cu), zinc (Zn), and iron (Fe), play critical role in disease progression. Because these transition metal ions are important for cellular function, their imbalance can cause oxidative stress that leads to cellular death and eventual cognitive decay. Importantly, these transition metal ions can interact with the amyloid-βprotein precursor (AβPP) and Aβ42 peptide, affecting Aβ aggregation and increasing its neurotoxicity. Considering how metal dyshomeostasis may substantially contribute to AD, this review discusses polyphenols and the underlying chemical principles that may enable them to act as natural chelators. Furthermore, polyphenols have various therapeutic effects, including antioxidant activity, metal chelation, mitochondrial function, and anti-amyloidogenic activity. These combined therapeutic effects of polyphenols make them strong candidates for a moderate chelation-based therapy for AD.
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http://dx.doi.org/10.3233/JAD-200185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809605PMC
June 2020

Reproducible molecular networking of untargeted mass spectrometry data using GNPS.

Nat Protoc 2020 06 13;15(6):1954-1991. Epub 2020 May 13.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.

Global Natural Product Social Molecular Networking (GNPS) is an interactive online small molecule-focused tandem mass spectrometry (MS) data curation and analysis infrastructure. It is intended to provide as much chemical insight as possible into an untargeted MS dataset and to connect this chemical insight to the user's underlying biological questions. This can be performed within one liquid chromatography (LC)-MS experiment or at the repository scale. GNPS-MassIVE is a public data repository for untargeted MS data with sample information (metadata) and annotated MS spectra. These publicly accessible data can be annotated and updated with the GNPS infrastructure keeping a continuous record of all changes. This knowledge is disseminated across all public data; it is a living dataset. Molecular networking-one of the main analysis tools used within the GNPS platform-creates a structured data table that reflects the molecular diversity captured in tandem mass spectrometry experiments by computing the relationships of the MS spectra as spectral similarity. This protocol provides step-by-step instructions for creating reproducible, high-quality molecular networks. For training purposes, the reader is led through a 90- to 120-min procedure that starts by recalling an example public dataset and its sample information and proceeds to creating and interpreting a molecular network. Each data analysis job can be shared or cloned to disseminate the knowledge gained, thus propagating information that can lead to the discovery of molecules, metabolic pathways, and ecosystem/community interactions.
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http://dx.doi.org/10.1038/s41596-020-0317-5DOI Listing
June 2020

Isolation and identification of sapotexanthin 5,6-epoxide and 5,8-epoxide from red mamey (Pouteria sapota).

Chirality 2020 05 3;32(5):579-587. Epub 2020 Mar 3.

Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary.

Two new carotenoids, sapotexanthin 5,6-epoxide and sapotexanthin 5,8-epoxide, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Sapotexanthin 5,6-epoxide was also prepared by partial synthesis via epoxidation of sapotexanthin, and the (5R,6S) and (5S,6R) stereoisomers were identified by high-performance liquid chromatography-electronic circular dichroism (HPLC-ECD) analysis. Spectroscopic data of the natural and semisynthetic derivatives obtained by acid-catalyzed rearrangement of cryptocapsin 5,8-epoxide stereoisomers were compared for structural elucidation.
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http://dx.doi.org/10.1002/chir.23206DOI Listing
May 2020

Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis.

Int J Mol Sci 2019 Nov 7;20(22). Epub 2019 Nov 7.

Center for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge 0843-01103, Panama.

Alzheimer's disease (AD) is the most devastating neurodegenerative disorder that affects the aging population worldwide. Endogenous and exogenous factors are involved in triggering this complex and multifactorial disease, whose hallmark is Amyloid-β (Aβ), formed by cleavage of amyloid precursor protein by β- and γ-secretase. While there is no definitive cure for AD to date, many neuroprotective natural products, such as polyphenol and carotenoid compounds, have shown promising preventive activity, as well as helping in slowing down disease progression. In this article, we focus on the chemistry as well as structure of carotenoid compounds and their neuroprotective activity against Aβ aggregation using molecular docking analysis. In addition to examining the most prevalent anti-amyloidogenic carotenoid lutein, we studied cryptocapsin, astaxanthin, fucoxanthin, and the apocarotenoid bixin. Our computational structure-based drug design analysis and molecular docking simulation revealed important interactions between carotenoids and Aβ via hydrogen bonding and van der Waals interactions, and shows that carotenoids are powerful anti-amyloidogenic molecules with a potential role in preventing AD, especially since most of them can cross the blood-brain barrier and are considered nutraceutical compounds. Our studies thus illuminate mechanistic insights on how carotenoids inhibit Aβ aggregation. The potential role of carotenoids as novel therapeutic molecules in treating AD and other neurodegenerative disorders are discussed.
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http://dx.doi.org/10.3390/ijms20225553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888440PMC
November 2019

Anti-amyloid aggregation activity of novel carotenoids: implications for Alzheimer's drug discovery.

Clin Interv Aging 2017 15;12:815-822. Epub 2017 May 15.

Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama, Republic of Panama.

Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 33.5 million people worldwide. Aging is the main risk factor associated with AD. Drug discovery based on nutraceutical molecules for prevention and treatment of AD is a growing topic. In this sense, carotenoids are phytochemicals present mainly in fruits and vegetables with reported benefits for human health. In this research, the anti-amyloidogenic activity of three carotenoids, cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin, was assessed. Cryptocapsin showed the highest bioactivity, while cryptocapsin-5,6-epoxide and zeaxanthin exhibited similar activity on anti-aggregation assays. Molecular modeling analysis revealed that the evaluated carotenoids might follow two mechanisms for inhibiting Aβ aggregation: by preventing the formation of the fibril and through disruption of the Aβ aggregates. Our studies provided evidence that cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin have anti-amyloidogenic potential and could be used for prevention and treatment of AD.
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http://dx.doi.org/10.2147/CIA.S134605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440000PMC
November 2017

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer's Disease.

J Alzheimers Dis 2017 ;60(s1):S59-S68

Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Republic of Panama.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Brain inflammation plays a key role in the progression of AD. Deposition of senile plaques in the brain stimulates an inflammatory response with the overexpression of pro-inflammatory mediators, such as the neuroinflammatory cytokine. interleukin-6. Curcumin has been revealed to be a potential agent for treating AD following different neuroprotective mechanisms, such as inhibition of aggregation and decrease in brain inflammation. We synthesized new curcumin derivatives with the aim of providing good anti-aggregation capacity but also improved anti-inflammatory activity. Nine curcumin derivatives were synthesized by etherification and esterification of the aromatic region. From these derivatives, compound 8 exhibited an anti-inflammatory effect similar to curcumin, while compounds 3, 4, and 10 were more potent. Moreover, when the anti-aggregation activity is considered, compounds 3, 4, 5, 6, and 10 showed biological activity in vitro. Compound 4 exhibited a strong anti-aggregation effect higher than curcumin. Monofunctionalized curcumin derivatives showed better bioactivity than difunctionalized compounds. Moreover, the presence of bulky groups in the chemical structure of curcumin derivatives decreased bioactivity.
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http://dx.doi.org/10.3233/JAD-170071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737775PMC
April 2018

Mechanistic insights into the potassium tert-butoxide-mediated synthesis of N-heterobiaryls.

Chem Commun (Camb) 2016 Aug;52(64):9945-8

Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249, USA.

We report herein that symmetrical and non-symmetrical N-heterobiaryls are produced by a potassium tert-butoxide-mediated dimerization of heterocyclic N-oxides. The reaction is scalable and transition metal-free, and can be carried out under thermal and microwave conditions. Preliminary mechanistic studies point to the involvement of radical anionic intermediates arising from the N-oxide substrates and potassium tert-butoxide.
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http://dx.doi.org/10.1039/c6cc04816aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109978PMC
August 2016

Experimental and mechanistic analysis of the palladium-catalyzed oxidative C8-selective C-H homocoupling of quinoline N-oxides.

Chem Commun (Camb) 2015 Jun;51(46):9507-10

Department of Chemistry, University of Texas at San Antonio, San Antonio, TX 78249, USA.

A novel site-selective palladium-catalyzed oxidative C8-H homocoupling reaction of quinoline N-oxides has been developed. The reaction affords substituted 8,8'-biquinolyl N,N'-dioxides that can be readily converted to a variety of functionalized 8,8'-biquinolyls. Mechanistic studies point to the crucial role of the oxidant and a non-innocent behavior of acetic acid as a solvent.
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http://dx.doi.org/10.1039/c5cc02227dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714569PMC
June 2015

Palladium-Catalyzed C8-Selective C-H Arylation of Quinoline -Oxides: Insights into the Electronic, Steric and Solvation Effects on the Site-Selectivity by Mechanistic and DFT Computational Studies.

ACS Catal 2015 Jan;5(1):167-175

Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, United States.

We report herein a palladium-catalyzed C-H arylation of quinoline -oxides that proceeds with high selectivity in favor of the C8-isomer. This site-selectivity is unusual for palladium, since all of the hitherto described methods of palladium-catalyzed C-H functionalization of quinoline -oxides are highly C2-selective. The reaction exhibits a broad synthetic scope with respect to quinoline -oxides and iodoarenes and can be significantly accelerated to sub-hour reaction times under microwave irradiation. The C8-arylation method can be carried out on gram scale and has excellent functional group tolerance. Mechanistic and Density Functional Theory (DFT) computational studies provide evidence for the cyclopalladation pathway and describe key parameters influencing the site-selectivity.
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http://dx.doi.org/10.1021/cs501813vDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286811PMC
January 2015

Polyphenols as therapeutic molecules in Alzheimer's disease through modulating amyloid pathways.

Mol Neurobiol 2015 Apr 15;51(2):466-79. Epub 2014 May 15.

Centre for Biodiversity and Drug Discovery, Institute for Scientific Research and High Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative condition. The complex pathology of this disease includes oxidative stress, metal deposition, formation of aggregates of amyloid and tau, enhanced immune responses, and disturbances in cholinesterase. Drugs targeted toward reduction of amyloidal load have been discovered, but there is no effective pharmacological treatment for combating the disease so far. Natural products have become an important avenue for drug discovery research. Polyphenols are natural products that have been shown to be effective in the modulation of the type of neurodegenerative changes seen in AD, suggesting a possible therapeutic role. The present review focuses on the chemistry of polyphenols and their role in modulating amyloid precursor protein (APP) processing. We also provide new hypotheses on how these therapeutic molecules may modulate APP processing, prevent Aβ aggregation, and favor disruption of preformed fibrils. Finally, the role of polyphenols in modulating Alzheimer's pathology is discussed.
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http://dx.doi.org/10.1007/s12035-014-8722-9DOI Listing
April 2015