Article
Biochemistry & Molecular Biology
Modesto de Candia, Alexander A. Titov, Antonio Viayna, Larisa N. Kulikova, Rosa Purgatorio, Brigida Piergiovanni, Mauro Niso, Marco Catto, Leonid G. Voskressensky, F. Javier Luque, Cosimo D. Altomare
Summary: This study investigated the inhibitory activity of newly synthesized derivatives on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compound 7c was found to be a highly potent and selective inhibitor of BChE, with a noncompetitive/mixed-type inhibition mechanism. The study also highlighted the structural factors that enhance inhibition potency and selectivity, as well as the differences between the binding sites of equine BChE and recombinant human BChE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Qi Li, Baichen Xiong, Yuanyuan Wang, Weiping Lyu, Shuaishuai Xing, Ying Chen, Qinghong Liao, Siyu He, Feng Feng, Wenyuan Liu, Yao Chen, Haopeng Sun
Summary: In this study, two potential candidates for treating neurodegenerative diseases, especially Alzheimer's disease, were selected and optimized based on their inhibitory activity and drug-like properties. These compounds exhibited significant inhibitory capacity and neuroprotective properties, and could potentially improve symptoms and nutritional status of AD patients. The findings provide important insights for the development of new drugs for AD.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
McLane J. Watson, Paolo D. A. Vignali, Steven J. Mullett, Abigail E. Overacre-Delgoffe, Ronal M. Peralta, Stephanie Grebinoski, Ashley V. Menk, Natalie L. Rittenhouse, Kristin DePeaux, Ryan D. Whetstone, Dario A. A. Vignali, Timothy W. Hand, Amanda C. Poholek, Brett M. Morrison, Jeffrey D. Rothstein, Stacy G. Wendell, Greg M. Delgoffe
Summary: T-reg cells exhibit broad heterogeneity in glucose metabolism within normal and transformed tissues, utilizing an alternative metabolic pathway to maintain their suppressive function and proliferation. Glucose uptake is correlated with poorer suppressive function and long-term instability, while high-glucose conditions impair T-reg cell function and stability. Additionally, T-reg cells upregulate pathways involved in the metabolism of lactic acid, with lactate uptake being dispensable for peripheral T-reg cells but required intratumorally for slowed tumor growth and increased response to immunotherapy.
Article
Biochemistry & Molecular Biology
Shuaishuai Xing, Ying Chen, Baichen Xiong, Weixuan Lu, Qi Li, Yuanyuan Wang, Mengxia Jiao, Feng Feng, Yao Chen, Wenyuan Liu, Haopeng Sun
Summary: 2513-4169, a promising lead compound, shows potential inhibitory activity and neuroprotective effect for treating Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Chemistry, Multidisciplinary
Wai Cheung Chan, Shabnam Sharifzadeh, Sara J. Buhrlage, Jarrod A. Marto
Summary: Covalent drugs are essential in modern medicine, and there has been a recent surge in interest in the development of covalent inhibitors, particularly utilizing mass spectrometry-based chemoproteomic methods. This review highlights the practical applications of these techniques in target identification, hit discovery, and lead characterization/optimization in covalent drug discovery, with case studies to demonstrate their real-world significance and future opportunities.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Wantida Chaiyana, Suwannee Sriyab, Siriporn Okonogi
Summary: This study investigated the chemical composition and inhibitory activity of Alpinia galanga essential oil (AGO) on acetylcholinesterase (AChE) compared to butyrylcholinesterase (BChE). The results showed that AGO exhibited superior inhibitory activity against AChE and the microemulsion form had even higher anticholinesterase activity, suggesting its potential as an alternative treatment for Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Ante Milicevic, Goran Sinko
Summary: This study developed QSAR models based on simple descriptors to estimate BChE inhibition potency of different compounds, achieving good correlation with certain topological and constitutional descriptors.
Article
Biochemistry & Molecular Biology
Ana Mercia Silva Mascarenhas, Raquel Bianca Marchesine de Almeida, Moyses Fagundes de Araujo Neto, Gessica Oliveira Mendes, Jorddy Neves da Cruz, Cleydson Breno Rodrigues dos Santos, Mariana Borges Botura, Franco Henrique Andrade Leite
Summary: This study aimed to identify promising dual inhibitors against hAChE and hBuChE using in silico approaches. By constructing pharmacophore models and conducting molecular docking experiments, several potential dual inhibitors against both enzymes were identified.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar, Gopichand Gutti, Pravin Gore, Bharat Sahu, Ashok Kumar, Sushil Kumar Singh
Summary: This study successfully designed and synthesized effective BChE inhibitors through machine learning, and their activity was verified through in silico and in vitro evaluations.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lupe Furtado-Alle, Luciane Tureck, Carolina S. de Oliveira, Joao V. M. Hortega, Ricardo L. R. Souza
Summary: Butyrylcholinesterase (BChE) is an enzyme found primarily in the liver, plasma, and brain, and it has been recognized for its role in the hydrolysis of choline esters. Recent studies have shown its involvement in lipid metabolism, suggesting it plays a crucial role in maintaining lipid homeostasis. However, the relationship between external factors and BChE activity in lipid metabolic pathways is still complex and requires further investigation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Shujing Xu, Lin Sun, Alexej Dick, Waleed A. Zalloum, Tianguang Huang, Megan E. Meuser, Xujie Zhang, Yucen Tao, Srinivasulu Cherukupalli, Dang Ding, Xiao Ding, Shenghua Gao, Xiangyi Jiang, Dongwei Kang, Erik De Clercq, Christophe Pannecouque, Simon Cocklin, Xinyong Liu, Peng Zhan
Summary: By modifying the structure of PF74, two potent compounds with significantly improved metabolic stability were identified, showing promising antiviral activity against both HIV-1 and HIV-2. These compounds represent a blueprint for developing a new generation of HIV treatment regimens with novel structures and enhanced metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Naghmana Kausar, Shahzad Murtaza, Muhammad Nadeem Arshad, Rahman Shah Zaib Saleem, Abdullah M. Asiri, Samia Kausar, Ataf Ali Altaf, Adina Tatheer, Ashraf Y. Elnaggar, Salah M. El-Bahy
Summary: A series of new hydrazone derivatives were synthesized and evaluated for their potential as anti-Alzheimer's agents, antioxidant activities, and cytotoxicity. Some compounds showed dual inhibition of AChE and BChE, with IC50 values comparable to the standard drug donepezil. Additionally, DFT and molecular docking studies supported the experimental findings.
Review
Agriculture, Multidisciplinary
Qiong Lu, Huijie Xie, Mingbo Qu, Tian Liu, Qing Yang
Summary: Sustainable agriculture requires selective insecticides, and the discovery of lepidopteran-specific molecular targets, such as the chitinase enzyme, can aid in the development of such insecticides. By understanding the biological function and crystal structure of the enzyme, as well as identifying small-molecule inhibitors, researchers have made progress in developing selective insecticides that are effective against lepidopteran pests but harmless to their natural enemies.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Niels Heise, Sander Friedrich, Veronika Temml, Daniela Schuster, Bianka Siewert, Rene Csuk
Summary: The study demonstrated that the acetylated triterpenoic acids could effectively inhibit the enzyme butyrylcholinesterase (BChE) while showing weak inhibition for acetylcholinesterase (AChE). Enzyme kinetics evaluation revealed hyperbolic inhibition for BChE, and molecular modeling explained the selectivity between AChE and BChE for these compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Megan E. Meuser, Poli Adi Narayana Reddy, Alexej Dick, Jean Marc Maurancy, Joseph M. Salvino, Simon Cocklin
Summary: The team employed a computational-driven workflow to design improved PF-74 analogs with enhanced metabolic stability for inhibiting HIV-1 infection. They were able to increase the metabolic stability by 204-fold in comparison to the parental compound in just three analog steps, demonstrating the effectiveness and efficiency of this new approach.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Catherine J. Byrne, Sean Egan, Jerome P. Fennell, Philomena O'Byrne, Helen Enright, Evelyn Deasy, Sheila A. Ryder, Deirdre M. D'Arcy, Johnny McHugh
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2015)
Article
Medicine, Research & Experimental
Susan Mary O'Dwyer, Elaine MacHale, Imran Sulaiman, Martin Holmes, Cian Hughes, Shona D'Arcy, Viliam Rapcan, Terence Taylor, Fiona Boland, Sinthia Bosnic-Anticevich, Richard B. Reilly, Sheila A. Ryder, Richard W. Costello
Article
Allergy
Imran Sulaiman, Jansen Seheult, Elaine MacHale, Shona D'Arcy, Fiona Boland, Katrina McCrory, John Casey, Gerard Bury, Mazen Al-Alawi, Susan O'Dwyer, Sheila A. Ryder, Richard B. Reilly, Richard W. Costello
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2016)
Article
Infectious Diseases
Catherine J. Byrne, Ted Parton, Brett McWhinney, Jerome P. Fennell, Philomena O'Byrne, Evelyn Deasy, Sean Egan, Helen Enright, Ronan Desmond, Sheila A. Ryder, Deirdre M. D'Arcy, Johnny McHugh, Jason A. Roberts
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2018)
Article
Biochemical Research Methods
C. G. Carolan, V. S. Lamzin
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
(2014)
Article
Biochemical Research Methods
Vitaly G. Grigorenko, Tatiana E. Petrova, Ciaran Carolan, Maya Yu Rubtsova, Igor Uporov, Joana Pereira, Grzegorz Chojnowski, Valeriya R. Samygina, Victor S. Lamzin, Alexey M. Egorov
Summary: This study presents novel crystal structures of the native beta-lactamase TEM-171 and its complexes with the inhibitor tazobactam. The results provide valuable insights for the rational design of new beta-lactamase inhibitors.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Geriatrics & Gerontology
Reham A. Kalim, Conal J. Cunningham, Sheila A. Ryder, Niamh M. McMahon
Summary: This study explores the factors that influence doctors when deprescribing fall-risk increasing drugs (FRIDs) in a hospital setting. The study finds that barriers to deprescribing include lack of time, incomplete patient records, medication changes initiated by other specialists, and difficulties in following up patients after discharge. Facilitators include enhanced documentation through electronic patient records, support from other healthcare professionals such as clinical pharmacists, and patients' engagement.
Article
Pharmacology & Pharmacy
Theo J. Ryan, Sheila A. Ryder, Deirdre M. D'Arcy, John M. Quigley, Nyin N. Ng, Wuey Q. Ong, Zhong H. Tey, Maire O'Dwyer, John J. Walsh
Summary: The study describes the design, implementation, and evaluation of a pharmacy-integrated learning component for year 1 students, using the WHO's analgesic ladder as a scaffold for case-based learning. The integrated cases were mapped to the national Core Competency Framework for Pharmacists in Ireland and the school's cross-cutting curricular integration themes, and delivered through peer-to-peer teaching to 68 first-year pharmacy students. Highlights from a student survey included recognition of the importance of core science knowledge, enabling integrated learning, and the suitability of the integrated component for entry-level students.
Article
Education, Scientific Disciplines
Theo J. Ryan, Eimear Ni Sheachnasaigh, Sheila A. Ryder
PHARMACY EDUCATION
(2020)
Article
Biochemistry & Molecular Biology
D. A. Beshnova, C. Carolan, V. G. Grigorenko, M. Yu Rubtsova, E. Gbekor, J. Lewis, V. S. Lamzin, A. M. Egorov
BIOCHEMISTRY MOSCOW-SUPPLEMENT SERIES B-BIOMEDICAL CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Theo J. Ryan, Tamasine Grimes, Martin C. Henman, Eimear Ni Sheachnasaigh, Maire O'Dwyer, Cicely Roche, Sheila A. Ryder, Astrid Sasse, John J. Walsh, Deirdre M. DArcy
Article
Infectious Diseases
C. J. Byrne, J. A. Roberts, B. McWhinney, S. A. Ryder, J. P. Fennell, P. O'Byrne, E. Deasy, S. Egan, R. Desmond, H. Enright, D. M. D'Arcy, J. McHugh
CLINICAL MICROBIOLOGY AND INFECTION
(2017)
Article
Microbiology
Catherine J. Byrne, Jason A. Roberts, Brett McWhinney, Jerome P. Fennell, Philomena O'Byrne, Evelyn Deasy, Sean Egan, Ronan Desmond, Helen Enright, Sheila A. Ryder, Deirdre M. D'Arcy, Johnny McHugh
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2017)
Article
Respiratory System
Imran Sulaiman, Jansen Seheult, Elaine MacHale, Fiona Boland, Susan M. O'Dwyer, Viliam Rapcan, Shona D'Arcy, Breda Cushen, Matshediso Mokoka, Isabelle Killane, Sheila A. Ryder, Richard B. Reilly, Richard W. Costello
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2016)
Article
Pharmacology & Pharmacy
Cathal A. Cadogan, Sheila A. Ryder
INTERNATIONAL JOURNAL OF PHARMACY PRACTICE
(2015)