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
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)
Article
Biochemistry & Molecular Biology
Sultan Darvesh, Scott Banfield, Maeve Dufour, Katrina L. Forrestall, Hillary Maillet, G. Andrew Reid, Dane Sands, Ian R. Pottie
Summary: The study aimed to determine whether the KR histochemical method could be used to evaluate probes at the site of pathology. The results suggest that the KR method may provide an efficient means to screen compounds as probes for imaging AD-associated ChEs.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Zeinab Faghih, Soghra Khabnadideh, Amirhossein Sakhteman, Ali Khohadel Shirazi, Hojat Allah Yari, Ali Chatraei, Zahra Rezaei, Sara Sadeghian
Summary: A series of novel carbazole-benzylpiperazine hybrids were synthesized and their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The results showed that the type of linker and substitutions greatly affected the inhibitory activity and selectivity of the compounds. Compound 7a with meta and para fluorine substitution exhibited the highest inhibitory activity against AChE, while compounds 7h and 7k with meta fluorine and meta methyl substitutions showed the strongest inhibition against BuChE. Kinetic analysis and molecular modeling studies revealed that compound 7e acted as a mixed-type inhibitor against AChE, interacting with both the catalytic active site and the peripheral anionic site.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Dawid Panek, Anna Pasieka, Gniewomir Latacz, Paula Zareba, Michal Szczech, Justyna Godyn, Fabien Chantegreil, Florian Nachon, Xavier Brazzolotto, Anna Skrzypczak-Wiercioch, Maria Walczak, Magdalena Smolik, Kinga Salat, Georg Hoefner, Klaus Wanner, Anna Wieckowska, Barbara Malawska
Summary: A highly selective hBuChE inhibitor (29) with potential benefits for treating Alzheimer's disease has been identified through extensive in vitro and in vivo evaluations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nguyen Manh Cuong, Pham Ngoc Khanh, Le Thi Hong Nhung, Nguyen Xuan Ha, Tran Thu Huong, Katarina Bauerova, Young Ho Kim, Do Dinh Tung, Trinh Thi Thuy, Nguyen Thi Hoang Anh
Summary: From the root bark of Pinus krempfii Lecomte, four flavonoids were isolated and evaluated for their inhibitory activities against AChE and BChE enzymes in vitro and in silico. Tectochrysin (1) showed the highest inhibition activity against AChE and formed stable complexes with the protein. Galangin (2) exhibited significant inhibitory activity against BChE and formed hydrogen bonds with the protein. The study provided new insights for drug discovery and the development of neuroprotective substances for Alzheimer's disease treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Nutrition & Dietetics
Qazi Mohammad Sajid Jamal, Mohammad Imran Khan, Ali H. H. Alharbi, Varish Ahmad, Brijesh Singh Yadav
Summary: Alzheimer's disease (AD), the most common type of dementia, is associated with memory and thinking problems. Flavonoids in apple have been identified as potential inhibitors for AD. This study found that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor for the treatment of AD and other neurological disorders.
Article
Biochemistry & Molecular Biology
Rosa Purgatorio, Nicola Gambacorta, Modesto de Candia, Marco Catto, Mariagrazia Rullo, Leonardo Pisani, Orazio Nicolotti, Cosimo D. Altomare
Summary: The study found that the direct thrombin inhibitor dabigatran is beneficial in animal models of Alzheimer's disease. Through the Multi-fingerprint Similarity Searching Algorithm, a new multimodal agent was identified, with the N-phenyl-1-(pyridin-4-yl)piperidine-4-carboxamide derivative 1 showing inhibitory activity against multiple enzymes and receptors.
Article
Biochemistry & Molecular Biology
Rosa Purgatorio, Nicola Gambacorta, Francesco Samarelli, Gianfranco Lopopolo, Modesto de Candia, Marco Catto, Orazio Nicolotti, Cosimo D. Altomare
Summary: This study explores the impact of the malonamide bridge on the enzyme inhibition potency of peptidomimetic inhibitors of coagulation factor Xa (fXa). Through the synthesis and testing of 23 malonamide derivatives, it was found that the malonamide linker significantly increases the anti-fXa potency and selectivity. Some of these compounds also show potential as neuroprotective agents for the treatment of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Kishan B. Patel, Dushyant Patel, Nirav R. Patel, Ashish M. Kanhed, Divya M. Teli, Bhumi Gandhi, Bhavik S. Shah, Bharat N. Chaudhary, Navnit K. Prajapati, Kirti Patel, Mange Ram Yadav
Summary: Carbazole-based derivatives were designed, synthesized, and evaluated for their inhibitory activity against cholinesterase, antioxidant properties, and metal chelating abilities. Two compounds showed promising ChE inhibitory activity and specific copper ion chelating ability, along with strong interactions with the active sites of ChE enzymes. These compounds also demonstrated significant in silico drug-like pharmacokinetic properties.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Noopur Khare, Sanjiv Kumar Maheshwari, Abhimanyu Kumar Jha
Summary: The study explores the potential of using compounds like Dihydroquercetin as inhibitors for Alzheimer's Disease by targeting Acetylcholinesterase and Butyrylcholinesterase. Molecular docking and dynamics simulations show promising binding patterns and stability, suggesting Dihydroquercetin as a good candidate for further therapeutic studies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Liping Guan, Dingxin Peng, Li Zhang, Jinjing Jia, Haiying Jiang
Summary: The marine environment is a rich source of functional materials, with seaweed containing potential compounds like liquiritigenin. In this study, derivatives based on liquiritigenin were synthesized and tested for their inhibitory effects on cholinesterases, showing potency against acetylcholinesterase and moderate to weak activity against butyrylcholinesterase. Kinetic studies revealed a dual binding site inhibition mechanism for compound 4o against AChE, and all tested compounds also displayed radical scavenging effects. The molecular docking simulation of 4o in the AChE active site correlated well with the pharmacological results.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemical Research Methods
Noelle A. Novales, Jason P. Schwans
Summary: In this study, the effects of commonly used cosolvents on two cholinesterases, AChE and BChE, were evaluated. Despite their structural similarities, AChE was found to be more sensitive to the organic cosolvents tested compared to BChE. The study also showed that the cosolvent effects may arise from the molecules acting as inhibitors.
ANALYTICAL BIOCHEMISTRY
(2022)
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
Chengyao Wu, Guijuan Zhang, Zai-Wei Zhang, Xia Jiang, Ziwen Zhang, Huanhuan Li, Hua-Li Qin, Wenjian Tang
Summary: Compound A10, as a selective BuChE inhibitor, exhibits neuroprotective effects, good safety profile, and can effectively restore Aβ (1-42)-induced cognitive dysfunction.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rudolf Vrabec, Jana Marikova, Miroslav Locarek, Jan Korabecny, Daniela Hulcova, Anna Hostalkova, Jiri Kunes, Jakub Chlebek, Tomas Kucera, Martina Hrabinova, Daniel Jun, Ondrej Soukup, Vincenza Andrisano, Jaroslav Jenco, Marcela Safratova, Lucie Novakova, Lubomir Opletal, Lucie Cahlikova
Summary: An undescribed indole alkaloid and twenty-two known compounds were isolated from aerial parts of Vinca minor L. The isolated alkaloids were identified using MS, HRMS, 1D, and 2D NMR techniques, with some revised NMR data. The (- )-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1Hindole showed significant inhibition activity against hBuChE and was studied further for its mode of inhibition and ability to cross the blood-brain barrier.
Article
Nutrition & Dietetics
Marcel Hrubsa, Tomas Siatka, Iveta Nejmanova, Marie Voprsalova, Lenka Kujovska Krcmova, Katerina Matousova, Lenka Javorska, Katerina Macakova, Laura Mercolini, Fernando Remiao, Marek Matus, Premysl Mladenka, OEMONOM
Summary: This review summarizes the current knowledge on essential vitamins B-1, B-2, B-3, and B-5, including their characteristics, sources, safety, therapeutic use, detection methods, food sources, and physiological functions.
Article
Biochemistry & Molecular Biology
Marcel Hrubsa, Raul Alva, Mst Shamima Parvin, Katerina Macakova, Jana Karlickova, Jaka Fadraersada, Lukas Konecny, Monika Moravcova, Alejandro Carazo, Premysl Mladenka
Summary: Flavonoids have positive cardiovascular effects, and one of its metabolites, 4-methylcatechol, is a potent antiplatelet compound. In this study, the activity of 22 compounds, including 4-methylcatechol and its derivatives, were compared. Results showed that 17 compounds were highly active in inhibiting platelet aggregation, with 7 of them having an IC50 below 3 mu M. These compounds showed no toxicity to erythrocytes or significant effects on blood coagulation.
Review
Medical Laboratory Technology
Jiri Janousek, Veronika Pilarova, Katerina Macakova, Anderson Nomura, Jessica Veiga-Matos, Diana Dias da Silva, Fernando Remiao, Luciano Saso, Katerina Mala-Ladova, Josef Maly, Lucie Novakova, Premysl Mladenka
Summary: Vitamin D plays a crucial role in calcium homeostasis and has various non-calcemic functions. Over one billion people worldwide are deficient in vitamin D, which is associated with several diseases. Supplementation can be beneficial, but it should be done under the supervision of healthcare professionals to avoid overdosing.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2022)
Article
Chemistry, Medicinal
Marcel Hrubsa, Khondekar Nurjamal, Alejandro Carazo, Nayana Nayek, Jana Karlickova, Lenka Applova, Indrajit Karmakar, Shamima Parvin, Jaka Fadraersada, Katerina Macakova, Premysl Mladenka, Goutam Brahmachari
Summary: In this study, the antiplatelet and anticoagulation properties of selected compounds were examined. Four out of 34 tested compounds showed equal or greater activity than the standard antiplatelet drug ASA. These compounds achieved their effects through antagonism at thromboxane receptors. The most active compound, 2-N, was 4-5 times more potent than ASA and holds promise for the development of novel antiplatelet drugs.
MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Martin Uher, Milos Hroch, Rozalie Perinova, Radim Havelek, Jana Kroustkova, Martina Rezacova, Darina Muthna, Darja Koutova, Jiri Kunes, Lucie Cahlikova
Summary: A new series of haemanthamine derivatives were designed and synthesized to enhance inhibitory effect on cancer cell proliferation and viability. Among them, derivative 21 showed enhanced antiproliferative effect, especially on HeLa, A549, and HT-29 cell lines. The cytotoxicity of derivative 21 was dose- and time-dependently suppressing cell proliferation and reducing cell survival compared to haemanthamine.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Food Science & Technology
Mst Shamima Parvin, Marcel Hrubsa, Jaka Fadraersada, Alejandro Carazo, Jana Karlickova, Lucie Cahlikova, Jakub Chlebek, Katerina Macakova, Premysl Mladenka
Summary: Isoquinoline alkaloids exhibit antiplatelet effects mainly at high concentrations, and bulbocapnine is a promising antiplatelet molecule.
Article
Biochemistry & Molecular Biology
Viriyanata Wijaya, Ondrej Jandourek, Jana Kroustkova, Katerina Hradiska-Breiterova, Jan Korabecny, Katerina Sobolova, Eliska Kohelova, Anna Hostalkova, Klara Konecna, Marcela Safratova, Rudolf Vrabec, Jiri Kunes, Lubomir Opletal, Jakub Chlebek, Lucie Cahlikova
Summary: A study found that alkaloids isolated from the plant Dicranostigma franchetianum showed moderate anti-tuberculosis activity, and further development and testing of semi-synthetic derivatives of these alkaloids showed significantly enhanced activity. All compounds exhibited lower cytotoxicity in a liver cancer cell line.
Review
Chemistry, Multidisciplinary
Michal Jurasek, Adolf Rybka, Lubomir Opletal, Pavel Drasar
Summary: Hops, as a component in various products such as drinks, food, cosmetics, and spice, contains a wide range of biologically active compounds. This plant has been highly regarded throughout history and may hold potential for pharmaceutical exploitation, including as a traditional folk medicine and a source of sedatives, estrogenic agents, antimicrobial substances, antidiabetic compounds, and cancerostatic agents.
Article
Biochemistry & Molecular Biology
Jana Kroustkova, Aneta Ritomska, Abdullah Al Mamun, Daniela Hulcova, Lubomir Opletal, Jiri Kunes, Lucie Cahlikova, Franz Bucar
Summary: A new isolated alkaloid, Narciindole A, was obtained from the bulbs of Narcissus pseudonarcissus. Its structure showed a similar structural motif as another known dimeric alkaloid, carltonine C. The biosynthetic pathway of dimeric carltonine-type alkaloids was proposed. However, the isolated alkaloids exhibited only moderate inhibition of human acetylcholinesterase and/or butyrylcholinesterase.
Article
Plant Sciences
Marcela Safratova, Jana Kroustkova, Negar Maafi, Daniela Suchankova, Rudolf Vrabec, Jakub Chlebek, Jiri Kunes, Lubomir Opletal, Franz Bucar, Lucie Cahlikova
Summary: Clivia miniata, endemic to South Africa and Swaziland, is one of the top-10 traded medicinal plants in informal medicine markets in South Africa. It contains various Amaryllidaceae alkaloids, some of which have been identified as having neuroenzyme inhibition activity.
Review
Biochemistry & Molecular Biology
Rudolf Vrabec, Gerald Blunden, Lucie Cahlikova
Summary: Alzheimer's disease is a common cause of dementia in the elderly population, but there is no effective treatment currently available. The increasing life expectancy worldwide is expected to lead to a significant rise in Alzheimer's disease rates, necessitating the urgent search for new drugs. Alkaloids, particularly harmine and isoquinoline alkaloids, show promise as multi-target compounds for Alzheimer's disease by inhibiting key enzymes involved in its pathophysiology. However, further research is needed to explore their mechanisms of action and develop potentially better synthetic analogues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Plant Sciences
A. Ritomska, J. Kroustkova, D. Hulcova, R. Havelek, L. Cahlikova
