Article
Medicine, Research & Experimental
Sagheer Ahmed, Sidrah Tariq Khan, Muhammad Kazim Zargaham, Arif Ullah Khan, Saeed Khan, Abrar Hussain, Jalal Uddin, Ajmal Khan, Ahmed Al-Harrasi
Summary: Alzheimer's disease is the most common type of dementia affecting the later years of life and will be a major burden on the healthcare system. Despite scientific advancements, there are still no therapies available to stop or slow the progression of the disease. FDA has approved certain drugs for AD treatment, but research also suggests potential benefits from herbal compounds.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Mehrdad Sadafi Kohnehshahri, Gholamabbas Chehardoli, Masoomeh Bahiraei, Tahmineh Akbarzadeh, Akram Ranjbar, Arezoo Rastegari, Zahra Najafi
Summary: The newly designed quinolotacrine hybrids showed promising inhibitory effects on AChE, with one compound exhibiting the best inhibitory activity. Additionally, these compounds demonstrated significant neuroprotective effects in in vitro experiments.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Eugenie Nepovimova, Lucie Svobodova, Rafael Dolezal, Vendula Hepnarova, Lucie Junova, Daniel Jun, Jan Korabecny, Tomas Kucera, Zuzana Gazova, Katarina Motykova, Jana Kubackova, Zuzana Bednarikova, Jana Janockova, Catarina Jesus, Luisa Cortes, Joao Pina, Danijela Rostohar, Carlos Serpa, Ondrej Soukup, Laura Aitken, Rebecca E. Hughes, Kamil Musilek, Lubica Muckova, Petr Jost, Marketa Chvojkova, Karel Vales, Martin Valis, Zofia Chrienova, Katarina Chalupova, Kamil Kuca
Summary: The series of tacrine-benzothiazole hybrids show promising anti-AChE properties and capability to block Aβ aggregation, with the most potent derivative being 10w that exhibits highly selective inhibition of AChE. Moreover, 10w also demonstrates strong inhibitory effects against ABAD activity.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Raquel B. M. de Almeida, Deyse B. B. Barbosa, Mayra R. R. do Bomfim, Jessika A. O. Amparo, Bruno S. S. Andrade, Silvia L. L. Costa, Joaquin M. Campos, Jorddy N. Cruz, Cleydson B. R. Santos, Franco H. A. Leite, Mariana B. B. Botura
Summary: The compound ZINC390718 was found to exhibit inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and showed low cytotoxicity in vitro. Molecular dynamics (MD) simulation revealed that ZINC390718 interacted with the catalytic residue sites of both enzymes. These findings suggest that ZINC390718 could be a potential chemotype for the development of new dual cholinesterase inhibitors.
Review
Chemistry, Multidisciplinary
Nicolas Navarro Martinez, Jorge Toledo Hernandez, Javier O. Morales
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease among the elderly, characterized by oxidative stress and the deposition of neurofibrillary tangles and A beta plaques. Natural antioxidants or ROS scavengers may prevent the formation of these aggregates, while A beta-degrading/anti-aggregating molecules could slow down AD progression. Traditional drugs for AD have limitations in crossing the blood-brain barrier. Nanocarrier conjugation of these drugs could enhance brain targeting and delivery, potentially delaying neurodegeneration in AD.
NANOTECHNOLOGY REVIEWS
(2023)
Article
Chemistry, Medicinal
Thierno Moussa Ndongo, Marieta L. C. Passos, Fernando Duraes, Diana I. S. P. Resende, Madalena Pinto, Emilia Sousa, Maria Lucia M. F. S. Saraiva
Summary: A miniaturized microsequential injection/lab-on-valve (mu SIA-LOV) system has been developed as a useful alternative for inhibitory studies on acetylcholinesterase, showing potential inhibitory effects higher than clinical agents at lower costs and reagent consumption. The system is robust, rapid, reliable, and easy to use.
ARCHIV DER PHARMAZIE
(2021)
Article
Medicine, General & Internal
Ayoub Farihi, Mohamed Bouhrim, Fatiha Chigr, Amine Elbouzidi, Noureddine Bencheikh, Hassan Zrouri, Fahd A. Nasr, Mohammad Khalid Parvez, Ahmad Alahdab, Ahmed Omar Touhami Ahami
Summary: This study examines the potential of seven medicinal herbs and phytochemicals as treatments for Alzheimer's Disease (AD). Through molecular docking and bioinformatics techniques, the compounds were found to have significant binding affinities with the human acetylcholinesterase enzyme and the ability to cross the blood-brain barrier. These findings suggest that these compounds may be effective oral medications for managing neurodegenerative disorders.
MEDICINA-LITHUANIA
(2023)
Article
Chemistry, Medicinal
Ignazio Schino, Mariangela Cantore, Modesto de Candia, Cosimo D. Altomare, Catarina Maria, Joao Barros, Vasco Cachatra, Patricia Calado, Karina Shimizu, Adilson A. Freitas, Maria C. Oliveira, Maria J. Ferreira, Jose N. C. Lopes, Nicola A. Colabufo, Amelia P. Rauter
Summary: Alzheimer's Disease (AD) is characterized by an imbalance in cholinergic neurotransmission, and the inhibition of acetylcholinesterase (AChE) and increase of butyrylcholinesterase (BChE) activity. Novel 6-benzamide purine nucleosides that selectively target BChE and possess chelating properties were synthesized. These compounds show potential as dual target compounds for the treatment of AD.
Article
Chemistry, Multidisciplinary
Saira Naseem, Ahmed Temirak, Aqeel Imran, Saquib Jalil, Shamool Fatima, Parham Taslimi, Jamshed Iqbal, Mussarat Tasleem, Muhammad Nawaz Tahir, Zahid Shafiq
Summary: In this study, new 1,3,4-oxadiazole derivatives were synthesized and tested as novel inhibitors of monoamine oxidase and cholinesterase enzymes. Several compounds showed promising inhibitory effects on these enzymes, with some compounds displaying multitargeting activity. These newly synthesized analogues represent potential lead compounds for the development of neurological disease treatments.
Review
Biochemistry & Molecular Biology
Marta Perez-Gomez Moreta, Natalia Burgos-Alonso, Maria Torrecilla, Jose Marco-Contelles, Cristina Bruzos-Cidon
Summary: The study confirmed a low efficacy of AChEI in improving cognitive symptoms of patients with mild to moderate AD, especially in cognitive aspects. However, AChEI showed better effects in improving the global state, with donepezil being the most effective treatment. Nonetheless, there was no evidence of improvement in behavioral disturbances with the use of AChEI.
Article
Biochemistry & Molecular Biology
Blazej Grodner, Mariola Napiorkowska, Dariusz Maciej Pisklak
Summary: This study evaluated the inhibition efficacy of four aminoalkanol derivatives on acetylcholinesterase in vitro. The results showed that the inhibitory potency of the derivatives varied depending on the nature of the substituents, with isopropylamine and/or methyl substituents being the most effective. Docking studies suggested that the compounds bind to the peripheral anionic site rather than entering the catalytic pocket.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Aravinda Babu, Mathew John, M. J. Liji, E. Maria, S. J. Bhaskar, B. K. Binukmar, Ayyiliath M. Sajith, Eeda Koti Reddy, K. V. Dileep, K. Sunil
Summary: Human acetylcholinesterase (hAChE) plays a potential role in acetylcholine management and AChE inhibitors have a significant impact in therapeutics. This study explored the active site geometry of hAChE upon binding to different ligands and discovered two prominent sub-pockets near the active site. Structural bioinformatics analysis identified 132 putative sub-pockets focused tacrine derivatives (SPFTDs) that showed stronger binding affinity than tacrine. The identification of these sub-pockets and SPFTDs provides new possibilities for future drug discovery targeting AChE in the treatment of Alzheimer's disease (AD).
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biology
Anushree Chandrashekhar Gade, Manikanta Murahari, Parasuraman Pavadai, Maushmi Shailesh Kumar
Summary: Alzheimer's disease is characterized by abnormal protein aggregation in the brain. This study focuses on identifying potential drugs from a comprehensive marine natural product database that can inhibit the enzyme responsible for this aggregation. Computational tools were used to screen and prioritize molecules based on their binding affinity and safety profiles.
Review
Biochemistry & Molecular Biology
Natalia Smyrska-Wieleba, Tomasz Mroczek
Summary: This article provides an updated description and comparison of natural inhibitors of cholinesterases (IChEs), namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), based on data from the last 15 years. It also highlights the potential impact of compound structures on the therapeutic effects of cholinesterase inhibitors. The findings suggest that natural sources are still promising for the discovery of new compounds with significant pharmacological activity, and further research is needed to understand the mechanisms of action and structure-activity correlation of cholinesterase inhibitors for medical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ashwani Arya, Rubal Chahal, Rekha Rao, Md. Habibur Rahman, Deepak Kaushik, Muhammad Furqan Akhtar, Ammara Saleem, Shaden M. A. Khalifa, Hesham R. El-Seedi, Mohamed Kamel, Ghadeer M. Albadrani, Mohamed M. Abdel-Daim, Vineet Mittal
Summary: Alzheimer's disease is a gradually growing irreversible illness of the brain that affects a large population worldwide, with potential treatment options involving inhibitors of acetylcholine (ACh) to improve cholinergic transmission.
Article
Chemistry, Inorganic & Nuclear
Neha Choudhary, Hayden Scheiber, Jiale Zhang, Brian O. Patrick, Maria de Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: A new octadentate chelator H(4)HBEDpa has been investigated for its chelation properties with trivalent metal ions, showing high metal-sequestering capacity for Fe3+ and susceptibility to hydrolysis for Ga3+ at higher pH. Density functional theory (DFT) calculations validated experimental findings, demonstrating tight binding of Fe(HBEDpa)- in an asymmetric pattern and the formation of octadentate complexes with larger metal ions like Lu3+.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tara E. Tracy, Jesus Madero-Perez, Danielle L. Swaney, Timothy S. Chang, Michelle Moritz, Csaba Konrad, Michael E. Ward, Erica Stevenson, Ruth Huttenhain, Grant Kauwe, Maria Mercedes, Lauren Sweetland-Martin, Xu Chen, Sue-Ann Mok, Man Ying Wong, Maria Telpoukhovskaia, Sang-Won Min, Chao Wang, Peter Dongmin Sohn, Jordie Martin, Yungui Zhou, Wenjie Luo, John Q. Trojanowski, Virginia M. Y. Lee, Shiaoching Gong, Giovanni Manfredi, Giovanni Coppola, Nevan J. Krogan, Daniel H. Geschwind, Li Gan
Summary: In this study, the researchers used APEX approach and AP-MS technique to characterize the Tau interactomes modified by neuronal activity and FTD mutations. They found that Tau interacts with presynaptic vesicle proteins and identified the binding sites. They also discovered that FTD mutations impair Tau's interaction with mitochondria proteins, which has important implications for the pathogenesis of AD.
Article
Chemistry, Multidisciplinary
Gokce Engudar, Cristina Rodriguez-Rodriguez, Narenda Kumar Mishra, Marta Bergamo, Guillaume J. Amouroux, Knud J. Jensen, Katayoun O. Saatchi, Urs O. Hafeli
Summary: This study found that the pharmacokinetics of insulin can be directly controlled with metal ions after covalent attachment of specific abiotic ligands. This provides new insights for exploring novel drug delivery strategies.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Neurosciences
Sarah M. Neuner, Maria Telpoukhovskaia, Vilas Menon, Kristen M. S. O'Connell, Timothy J. Hohman, Catherine C. Kaczorowski
Summary: This review explores the insights gained from both human and animal studies regarding resilience in Alzheimer's disease, and highlights future approaches to translating these insights into therapeutics.
TRENDS IN NEUROSCIENCES
(2022)
Article
Nanoscience & Nanotechnology
Colin Blackadar, Ka-Yee Grace Choi, Mary F. Embree, Heather M. Hennkens, Cristina Rodriguez-Rodriguez, Robert E. W. Hancock, Katayoun Saatchi, Urs O. Hafeli
Summary: Single-photon emission computed tomography (SPECT) is a useful tool for noninvasively visualizing the biodistribution of silver-containing compounds in rodents. The study found that antimicrobial silver nanoparticles, formed by neutron irradiation of palladium foil, can be stably incorporated into the lungs of mice without significant uptake in other organs. In a mouse model of pulmonary Pseudomonas aeruginosa infection, the nanoparticles effectively reduced bacterial burden without inducing excessive inflammation.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Inorganic & Nuclear
Aidan Ingham, Luke Wharton, Tarek El Sayed, Lily Southcott, Brooke L. McNeil, Maria B. Ezhova, Brian O. Patrick, Maria de Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: A new chelator H(2)ampa was designed and synthesized as a potential radiopharmaceutical chelator. The study investigated its coordination behavior with radioactive metals and found that H(2)ampa can effectively coordinate Bi3+, Pb2+, and La3+ ions to form metal complexes, demonstrating its potential application in radiopharmaceutical labeling.
INORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Tullio V. F. Esposito, Cristina Rodriguez-Rodriguez, Colin Blackadar, Evan F. Haney, Daniel Pletzer, Robert E. W. Hancock, Katayoun Saatchi, Urs O. Hafeli
Summary: This study investigated the pharmacokinetics of a well-characterized IDR molecule, IDR-1018. The distribution and clearance of the peptide were found to vary depending on the route of administration and dose. The study also revealed that local administration could avoid peptide toxicity associated with systemic administration.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Engineering, Biomedical
Helena Koniar, Cristina Rodriguez-Rodriguez, Valery Radchenko, Hua Yang, Peter Kunz, Arman Rahmim, Carlos Uribe, Paul Schaffer
Summary: This study evaluated the performance of Ac-226 imaging using quantitative SPECT imaging and presented the first-ever Ac-226 SPECT images. The results showed the feasibility of preclinical imaging with Ac-226, which demonstrated high resolution. The HEUHR collimator was recommended for imaging the activity distribution of Ac-226 in small animals.
PHYSICS IN MEDICINE AND BIOLOGY
(2022)
Article
Biochemical Research Methods
Luke Wharton, Chengcheng Zhang, Jutta Zeisler, Cristina Rodriguez-Rodriguez, Maryam Osooly, Valery Radchenko, Hua Yang, Kuo-Shyan Lin, Francois Benard, Paul Schaffer, Chris Orvig
Summary: A new, highly stable bifunctional ligand has been synthesized and studied for its complexation with [225Ac]Ac3+ and [111In]In3+ for radiopharmaceutical applications. The ligand showed effective complexation, high stability, and potential applications in 225Ac/111In theranostics.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Behavioral Sciences
Thomas J. Murdy, Amy R. Dunn, Surjeet Singh, Maria A. Telpoukhovskaia, Shanrong Zhang, Jacqueline K. White, Itamar Kahn, Marcelo Febo, Catherine C. Kaczorowski
Summary: In AD patients and mouse models, certain neurological features known as brain reserve may protect against AD-related cognitive decline. The genetic underpinnings of brain reserve and brain microstructure, which can be measured with dMRI, may advance AD treatment in diverse populations. By studying genetically diverse AD mice, we found that strain is the primary factor influencing brain microstructure and that memory is influenced by strain, sex, and 5XFAD genotype interactions.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Luke Wharton, Scott W. McNeil, Helen Merkens, Zheliang Yuan, Michiel van de Voorde, Gokce Engudar, Aidan Ingham, Helena Koniar, Cristina Rodriguez-Rodriguez, Valery Radchenko, Maarten Ooms, Peter Kunz, Francois Benard, Paul Schaffer, Hua Yang
Summary: Terbium radioisotopes (Tb-149, Tb-152, Tb-155, Tb-161) possess all four relevant nuclear decay modalities for theranostic radiopharmaceuticals. This study developed crown-TATE as a peptide-conjugate for radiolabeling with Tb-155 and Tb-161, and evaluated their imaging and pharmacokinetic properties in tumor-bearing mice. The radiotracers showed high tumor targeting and minimal retention in non-target organs, suggesting the potential of crown-TATE for molecular imaging and radionuclide therapy.
Article
Chemistry, Multidisciplinary
Lennart Bohrmann, Tobias Burghardt, Cristina Rodriguez-Rodriguez, Matthias M. Herth, Katayoun Saatchi, Urs O. Hafeli
Summary: This study presents a modular conjugation strategy based on click chemistry for the modification of high molecular weight hyperbranched polyglycerol (HPG) with sgc8 aptamer, fluorescent dyes, and In-111. The results indicate strong affinity of sgc8 against solid tumor-derived cell lines, but nonspecific uptake of scrambled ssDNA-functionalized HPG in cells highlights inherent challenges of aptamer-targeted probes. The study validates HPG-sgc8 as a nontoxic nanoprobe with high affinity against breast and lung cancer cells, and shows increased stability compared to free sgc8.
Article
Chemistry, Inorganic & Nuclear
Aidan Ingham, Thomas Kostelnik, Brooke L. McNeil, Brian O. Patrick, Neha Choudhary, Maria De Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: Amide-based chelators DTPAm, EGTAm, and ampam were synthesized and studied for their coordination properties with [Pb-nat/203]Pb2+ ions using H-1 NMR spectroscopy and X-ray diffraction. Results showed that DTPAm exhibited higher stability and activity, making it a promising candidate for [Pb-203/212]Pb2+-based radiopharmaceutical applications, while EGTAm and ampam showed lower performance and were deemed unsuitable for similar applications.
DALTON TRANSACTIONS
(2021)
Article
Endocrinology & Metabolism
Yunyun Di, Ellen K. Wasan, Jacqueline Cawthray, Jaweria Syeda, Munawar Ali, David M. L. Cooper, Ahmad Al-Dissi, Nima Ashjaee, Wubin Cheng, James Johnston, David M. Weekes, Thomas I. Kostelnik, Chris Orvig, Kishor M. Wasan
Summary: In this study, the efficacy and toxicity of a novel lanthanum compound, La (XT), in an ovariectomized rat model of osteoporosis were evaluated. The treatment did not show kidney or liver toxicities, and increased trabecular bone stiffness.
Article
Chemistry, Multidisciplinary
Neha Choudhary, Kendall E. Barrett, Manja Kubeil, Valery Radchenko, Jonathan W. Engle, Holger Stephan, Maria De Guadalupe Jaraquemada-Pelaez, Chris Orvig
Summary: The study investigated the affinity of the bisoxine hexadentate chelating ligand H(3)glyox for Mn2+, Cu2+, and Lu3+ ions, revealing different thermodynamic stabilities of the three metal complexes with Cu2+ being the highest and Mn2+ the lowest. DFT calculations showed distinct geometries and coordination preferences of these metal ions in the complexes, with potential implications for further investigations in Mn-52g/55-based bimodal imaging.