Article
Biochemistry & Molecular Biology
Matthew K. Craft, Grover L. Waldrop
Summary: The rise of antibacterial-resistant bacteria is a major problem globally, requiring novel antibacterial agents to combat. Acetyl-CoA carboxylase (ACC) is a validated target, and SABA1 represents a potentially new class of antibiotics that can be used to combat the antibacterial resistance crisis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Stepnik, Wirginia Kukula-Koch, Wojciech Plazinski, Kinga Gawel, Katarzyna Gawel-Beben, Daariimaa Khurelbat, Anna Boguszewska-Czubara
Summary: The aim of the study was to evaluate the inhibitory potential of triterpenoid saponins (astragalosides) from Astragalus mongholicus roots on acetylcholinesterase. TLC bioautography was used to identify the most potent astragalosides II, III and IV (with IC50 values of 5.9 mu M, 4.2 mu M, and 4.0 mu M, respectively). Molecular dynamics simulations showed strong affinity of astragalosides for blood-brain barrier models. The correlation between experimentally-determined IC50 values and theoretically-predicted binding energies was found to be 0.956.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mohammed Alrouji, Debarati DasGupta, Ghulam Md. Ashraf, Anwar L. Bilgrami, Fahad A. Alhumaydhi, Waleed Al Abdulmonem, Moyad Shahwan, Abdulrhman Alsayari, Akhtar Atiya, Anas Shamsi
Summary: This study evaluates the inhibitory potential of Huperzine A (HpA), an acetylcholinesterase inhibitor (AChEI), on MARK4. Molecular docking and molecular dynamics simulation show that the complex formed by HpA and MARK4 is structurally stable, and HpA effectively inhibits the kinase activity of MARK4.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Physical
Faiz Rasool, Muhammad Khalid, Muhammad Yar, Khurshid Ayub, Muhammad Tariq, Ajaz Hussain, Mehreen Lateef, Muhammad Kashif, Sana Iqbal
Summary: Two new chalcones were synthesized and studied for their interaction with DNA, urease inhibition, antioxidant potential, and drug discovery potential. Computational and experimental methods were used to investigate their properties and interactions, showing promising results for further drug development.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Physical
Aynur Alizada, Hakan Arslan
Summary: The compound 1-(4-chloro-benzoyl)-3-(2-trifluoromethyl-phenyl)thiourea was synthesized and its structure was determined using various techniques. The crystal structure analysis revealed important contributions to crystal packing from different interactions. The density functional theory method was employed to further analyze the compound's properties. Docking studies were also conducted to evaluate its inhibitory action against a key protease of COVID-19. Rating: 7/10
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Rochelly da Silva Mesquita, Andrii Kyrylchuk, Anton Cherednichenko, Ingrity Suelen Costa Sa, Lilian Macedo Bastos, Felipe Moura Araujo da Silva, Rita de Cassia Saraiva Nunomura, Andriy Grafov
Summary: This study isolated cholinesterase inhibitors from a plant species in the Amazon rainforest and investigated their interaction with cholinesterase enzymes using molecular docking and dynamics. The compounds demonstrated inhibitory effects on the enzymes and the in vitro results supported the in silico findings.
Article
Plant Sciences
Nguyen Ngoc Tuan, Huong Nguyen Thi, Chau Le Thi My, Tang Xuan Hai, Hieu Tran Trung, Anh Nguyen Thi Kim, Thanh Nguyen Tan, Tan Le Van, Cuong Quoc Nguyen, Quang De Tran, Ping-Chung Kuo, Quang Le Dang, Tran Dinh Thang
Summary: The phytochemical constituents from the roots of Millettia speciosa were analyzed and characterized, resulting in the identification of 10 compounds with potential pharmacological activities against inflammation and diabetes. The isolated compounds showed inhibitory effects on NO production and alpha-glucosidase, indicating their anti-inflammatory and anti-diabetic properties. Molecular docking studies revealed the better binding affinity and interactions of compounds 4, 5, and 10 with the target enzyme, suggesting their potential as lead molecules for drug development.
Article
Biochemistry & Molecular Biology
Seda Onder, Suat Sari, Ozden Tacal
Summary: The study investigated the inhibitory effects and mechanisms of the synthetic phenazine dye SO on human cholinesterases, demonstrating different inhibitory patterns on BChE, AChE, and BChE mutants. SO was found to be a potent inhibitor and may hold potential for the development of new drugs for AD treatment.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Sajjad Ahmad, Momin Khan, Muhammad Ishaq Ali Shah, Mahboob Ali, Aftab Alam, Muhammad Riaz, Khalid Mohammed Khan
Summary: In this study, 28 acyl hydrazones of flurbiprofen were synthesized and evaluated for their inhibitory activity against the urease enzyme. The compounds showed good inhibitory activities, with compound 30 being the most active. Furthermore, electron-donating groups on the phenyl ring were found to play a significant role in enzyme inhibition.
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Zhangeldy S. Nurmaganbetov, Serik D. Fazylov, Oralgazy A. Nurkenov, Andrei I. Khlebnikov, Tulegen M. Seilkhanov, Anarkul S. Kishkentaeva, Elvira E. Shults, Mark T. Quinn
Summary: Alzheimer's disease is a common neurodegenerative disease characterized by memory loss and cognitive impairment. The loss of cholinergic neurons is one of the main causes of this disease. Current acetylcholinesterase inhibitors have limitations, so there is ongoing research to find more effective inhibitors. In this study, new lupinine triazole derivatives were synthesized and evaluated for their inhibitory activity. The most promising compound showed mixed-type inhibition and molecular docking studies revealed the interaction between the compound and the target enzyme. A structure-activity relationship model was also developed to guide the design of more potent inhibitors.
Article
Cell Biology
Danish Iqbal, M. Salman Khan, Mohd Waiz, Md Tabish Rehman, Mohammed Alaidarous, Azfar Jamal, Abdulaziz S. Alothaim, Mohamed F. AlAjmi, Bader Mohammed Alshehri, Saeed Banawas, Mohammed Alsaweed, Yahya Madkhali, Abdulrahman Algarni, Suliman A. Alsagaby, Wael Alturaiki
Summary: Geraniol is a competitive inhibitor of AChE with a high binding affinity, as shown by in vitro and in silico studies. Docking and molecular dynamics simulations confirmed the stable conformation of geraniol in the binding cavity of AChE, suggesting its potential as a natural compound for neurological and neuromuscular disorders.
Article
Medicine, Research & Experimental
Karina Sierra, Jean Paulo de Andrade, Luciana R. Tallini, Edison H. Osorio, Osvaldo Yanez, Manuel Isaias Osorio, Nora H. Oleas, Olimpo Garcia-Beltran, Warley de S. Borges, Jaume Bastida, Edison Osorio, Natalie Cortes
Summary: This study isolated and described the alkaloids of Zephyranthes carinata Herb., finding galanthine as the main component with significant inhibitory activity against acetylcholinesterase. Molecular dynamics analysis revealed that galanthine interacts with the peripheral anionic binding site of the enzyme, preventing the entrance and exit of molecules from the active site. This research provides important information for the search of new cholinesterase inhibitors by identifying unknown bio-interactions between bioactive compounds and biological targets.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Nutrition & Dietetics
Nancy D. Asen, Ogadimma D. Okagu, Chibuike C. Udenigwe, Rotimi E. Aluko
Summary: This study explores the potential of peptides obtained from enzymatic digestion of pea protein as novel AChE-inhibitory agents in Alzheimer's disease management. The peptides were found to be able to change the conformation of AChE protein and inhibit its activity, making them promising candidates for more effective and safer AD treatments.
FRONTIERS IN NUTRITION
(2022)
Article
Pharmacology & Pharmacy
Monika Kadela-Tomanek, Maria Jastrzebska, Elwira Chrobak, Ewa Bebenek
Summary: Lipophilicity is an important property of potential drugs, as it affects their solubility, cell membrane penetration, and various pharmacokinetic processes. This study focused on the lipophilicity and other properties of quinolone-1,4-quinone hybrids. Experimental and theoretical methods were used to determine the lipophilicity, and the relationship between the nitrogen atom and lipophilicity was investigated. The bioavailability, neurotoxicity, and interaction with biological targets were also evaluated. The results showed that the hybrids had low lipophilicity, can be used orally, and have the ability to inhibit the BCL-2 protein.
Article
Chemistry, Physical
C. Sivakumar, V. Balachandran, B. Narayana, Vinutha V. Salian, B. Revathi, N. Shanmugapriya, K. Vanasundari
Summary: The compound CCPPE was studied for its structure, charge exchange, vibrational spectra, and antimicrobial activity performances.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Veena S. Kumar, Y. Sheena Mary, Y. Shyma Mary, Martin Kratky, Jarmila Vinsova, Cecilia Baraldi, M. S. Roxy, Maria Cristina Gamberini
Summary: By conducting spectroscopic analysis and SERS studies on different silver colloids, particular chemical properties of the CHTB molecule were identified, including significant shifts in Raman and SERS wavenumbers. Additionally, concentration-dependent SERS spectra revealed changes in molecular orientation. Molecular docking studies suggested potential value of CHTB in designing other pharmaceutical applications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Pharmacology & Pharmacy
Lilla Borbala Horvath, Martin Kratky, Vaclav Pflegr, Elod Mehes, Gergo Gyulai, Gergely Kohut, Akos Babiczky, Beata Biri-Kovacs, Zsuzsa Baranyai, Jarmila Vinsova, Szilvia Bosze
Summary: In this study, novel derivatives of 4-aminosalicylic acid were designed and evaluated by conjugating them to tuftsin peptides for intracellular efficacy and selectivity. The peptide conjugates showed preserved antimycobacterial activity against M. tuberculosis and displayed selectivity towards different host cells.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Vaclav Pflegr, Sarka Stepankova, Katarina Svrckova, Marketa Svarcova, Jarmila Vinsova, Martin Kratky
Summary: 2,5-Disubstituted 1,3,4-oxadiazoles are versatile scaffolds in medicinal chemistry that exhibit diverse biological activities. Decorated with dodecyl and interacting with AChE and BChE, these oxadiazole derivatives demonstrate moderate dual inhibition, showing potential as inhibitors for the treatment of dementias and myasthenia gravis.
Article
Chemistry, Medicinal
Vaclav Pflegr, Jirina Stolarikova, Jarmila Vinsova, Martin Kratky
Summary: A total of 23 N-(cyclo)alkyl-2-(2-isonicotinoylhydrazineylidene)propanamides and their analogues were designed, synthesized, and evaluated as potential antimycobacterial compounds. These compounds showed low minimum inhibitory concentrations (MIC) against both Mycobacterium tuberculosis and nontuberculous mycobacteria, and exhibited even lower MIC values compared to parent isonicotinohydrazide.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Martin Kratky, Peter Sramel, Pavol Bodo, Marta Soltesova Prnova, Lucia Kovacikova, Magdalena Majekova, Jarmila Vinsova, Milan Stefek
Summary: Aldose reductase, a key drug target in therapy of diabetic complications, can be inhibited by a series of six novel rhodanine based inhibitors. The compounds showed strong aldose reductase inhibitory activities with IC50 values ranging from 20 nM to 2000 nM. In silico docking revealed that the compounds interact with the anion-binding sub-pocket of aldose reductase through a deprotonated 4-hydroxyben-zylidene group, forming strong H-bond and charge interactions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Neto-Honorius Houngbedji, Sarka Stepankova, Vaclav Pflegr, Katarina Svrckova, Marketa Svarcova, Jarmila Vinsova, Martin Kratky
Summary: Based on previous reports, 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The compounds showed dual inhibition of both enzymes, with better or comparable inhibition than the drug rivastigmine. Molecular docking revealed the possible conformation of the compounds and their interactions with target enzymes, suggesting their potential as therapeutic agents.
Article
Chemistry, Medicinal
Martin Kratky, Klara Konecna, Adela Simkova, Ondrej Jandourek, Jana Maixnerova, Jirina Stolarikova, Marcela Vejsova, Barbora Voxova, Frantisek Trejtnar, Jarmila Vinsova
Summary: Twenty-one mafenide-based compounds were synthesized and tested for antimicrobial activity, showing promising efficacy against various pathogens including superbugs. Most imines of mafenide were bactericidal and retained activity against drug-resistant strains. The most promising drug candidates have iodinated salicylidene and 5-nitrofuran/thiophene-methylidene scaffolds.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Jamelah S. Al-Otaibi, Y. Sheena Mary, Y. Shyma Mary, Martin Kratky, Jarmila Vinsova, Maria Cristina Gamberini
Summary: SERS was used to study the surface adsorption of a benzohydrazide derivative on silver nanoparticles. The vibrational assignments in the SERS spectra at different concentrations were determined using density functional theory (DFT) calculations. The adsorption of the benzohydrazide derivative on the silver surface occurs through the p-electrons of the ring. The thermodynamic analysis suggests that the adsorption process is spontaneous and exothermic.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Chemistry, Physical
Jamelah S. Al-Otaibi, Y. Sheena Mary, Y. Shyma Mary, Martin Kratky, Jarmila Vinsova, Jineetkumar Gawad, Maria Cristina Gamberini
Summary: In this study, the infrared (IR), Raman and surface-enhanced Raman scattering (SERS) spectra of (Z)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carboximidamide hydrochloride (OHC) at different concentrations were investigated experimentally and using density functional theory (DFT) simulations. The structure of the OHC-Ag6 complex was optimized and it was found to exhibit charge transfer interaction (CTI) between Ag and OHC. The chemisorption of the molecule on Ag6 was confirmed through SERS investigation. The findings show the potential for engineering robust SERS active substrates for OHC-related biosensors.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Physical
Jamelah S. Al-Otaibi, Y. Sheena Mary, Y. Shyma Mary, Martin Kratky, Jarmila Vinsova, Maria Cristina Gamberini
Summary: SERS and vibrational spectroscopic studies of N-butyl-2-isonicotinoylhydrazine-1-carboxamide (INC) at different concentrations are reported. DFT calculations based on a silver cluster model and TD-DFT calculations support the experimental findings. Raman band enhancements in some SERS spectra suggest the contribution of charge transfer interactions to the overall enhancement of INC's Raman modes. The presence of inactive nR bands in the SERS spectrum indicates the chemisorption nature of INC with the silver surface in an inclined orientation according to selection rules. This study establishes a method for accurately quantifying INC and has potential applications in structurally relevant medications.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Jamelah S. Al-Otaibi, Yohannan Sheena Mary, Y. Shyma Mary, Martin Kratky, Jarmila Vinsova, Maria Cristina Gamberini
Summary: Surface enhanced Raman scattering (SERS) experiments were conducted to analyze the adsorption and orientation of BTB on silver colloid, and the results were compared with normal Raman spectra. Density functional theory (DFT) analysis validated the observed spectra of BTB. The BTB molecule interacts with Ag-6 clusters through atoms O-9, F-22, and Br-17 with an energy of -10.67 eV, confirmed by Frontier Molecular Orbitals (FMOs) study. SERS spectral analysis confirmed the tilted orientation of BTB on silver, which was theoretically justified.
Article
Chemistry, Medicinal
Urte Sachleviciute, Gabriel Gonzalez, Marie Kvasnicova, Sarka Stepankova, Neringa Kleiziene, Aurimas Bieliauskas, Marek Zatloukal, Miroslav Strnad, Frank A. Slok, Miroslav Kvasnica, Algirdas Sackus, Asta Zukauskaite
Summary: A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was synthesized and evaluated for neuroprotective activity in salsolinol- and glutamate-induced neurodegeneration models. Compound 28 showed the highest neuroprotective effect, which may be driven by reductions in oxidative stress and caspase-3/7 activity.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Inorganic & Nuclear
Giulio Bresciani, Jan Vanco, Tiziana Funaioli, Stefano Zacchini, Tomas Malina, Guido Pampaloni, Zdenek Dvorak, Zdenek Travnicek, Fabio Marchetti
Summary: Diruthenacyclopentenone complexes were synthesized and characterized. The complexes exhibited stronger cytotoxicity than cisplatin against various cancer cell lines, with the 17α-estradiol derived complex showing the highest activity. Further studies revealed that some complexes affected the cell cycle, apoptosis, oxidative stress, and autophagy.
INORGANIC CHEMISTRY
(2023)