Article
Biochemistry & Molecular Biology
Suzane Quintana Gomes, Leonardo Bruno Federico, Guilherme Martins Silva, Carla Duque Lopes, Sergio de Albuquerque, Carlos Henrique Tomich de Paula da Silva
Summary: Chagas disease is a well-known Neglected Tropical Disease that has spread beyond its endemic area. Due to the ineffectiveness and side effects of current treatments, this study explores novel drug candidates through the proteasome of Trypanosoma cruzi and drug repurposing using computational methodologies. Protein homology modeling was used to build a robust model, followed by virtual screening, toxicity predictions, and molecular docking. Three drugs were selected based on their favorable interactions and further validated through molecular dynamics simulations and biological assays.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Xi Gu, Ying Wang, Hanxun Wang, Hairui Wu, Wei Li, Jian Wang, Ning Li
Summary: This study utilized computational methods to build the structure of ETAR and predict its binding patterns with antagonists, identifying potential ETAR antagonists. Through virtual screening of a Traditional Chinese Medicine database, six compounds with the best binding energies were screened out, providing new therapeutic approaches for treating PAH.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Pankaj Pandey, Shamba Chatterjee, Tomayo Berida, Robert J. Doerksen, Sudeshna Roy
Summary: By using a homology model-based virtual screening approach combined with ligand-based e-pharmacophore screening, this study identified 15 potential antibacterial hits that could serve as new MraY inhibitors for tuberculosis treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Changyong Deng, Xiaobo Wang, Tangle Wang, Wei Liu, Xiaolan Yuan, Yan Huang, Shuang Cao
Summary: In this study, compound 4 was identified as a promising drug candidate against the drug-resistant influenza virus strain M2-V27A/S31N. Molecular dynamics simulation showed that compound 4 had stability and flexibility when binding to the target protein. The calculated binding free energy was -106.525 kcal/mol. Physicochemical and pharmacokinetic profiles predicted good bioavailability for compound 4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemical Research Methods
Bin Liu, Wei Zhang, Sheng Guo, Zhili Zuo
Summary: TRPC5 channel plays crucial roles in various physiological systems, but the evidence of its function is limited. In this study, potential hTRPC5 modulators were identified through virtual screening and molecular dynamics simulations, providing novel insights for the study and treatment of TRPC5-associated diseases.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Biochemistry & Molecular Biology
Shilpi Sarkar, Thirukumaran Kandasamy, Rajib Shome, Siddhartha Sankar Ghosh
Summary: This study highlights the involvement of epigenomic reprogramming and the role of p300 in breast cancer. By using virtual screening and molecular docking, two potential repurposed drugs, Netarsudil and Imatinib, were identified as inhibitors of p300 activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Shraddha Parate, Vikas Kumar, Jong Chan Hong, Keun Woo Lee
Summary: This study explores the clinical application of PP121, a dual inhibitor of serine/threonine and tyrosine kinases, as a therapeutic target. Through computational methods, two compounds (STOCK1N-98911 and STOCK1N-84953) were discovered to bind to mTOR and RET kinases with favorable interactions. This provides a preliminary platform for future experimental research and the development of dual inhibitors of serine/threonine and tyrosine kinases.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Jose Pena-Guerrero, Celia Fernandez-Rubio, Aroia Burguete-Mikeo, Rima El-Dirany, Alfonso T. Garcia-Sosa, Paul Nguewa
Summary: This study validates the Lmj_04_BRCT domain as a novel therapeutic target in Leishmania spp. and identifies CPE2 as a potential treatment option with significant activity against the parasites. In vitro and in silico studies suggest that CPE2 could be a promising new drug for leishmaniasis treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Shuoyan Tan, Xiaoqing Gong, Huanxiang Liu, Xiaojun Yao
Summary: LRRK2 kinase activity inhibition is an important therapeutic approach for Parkinson's disease, and this study successfully identified and validated two novel LRRK2 inhibitors through virtual screening and experimental assays, indicating their potential for PD therapy.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Chemistry, Multidisciplinary
Alejandro Varela-Rial, Maciej Majewski, Gianni De Fabritiis
Summary: Virtual screening methods, such as molecular docking and physical-based molecular simulations, offer different advantages and limitations in drug discovery. While molecular docking provides fast results using approximations, physical-based simulations offer more accurate models but require expensive computing infrastructure. Both approaches are useful for solving different aspects of the drug discovery process.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Andrea Dodaro, Matteo Pavan, Stefano Moro
Summary: The latest outbreak of monkeypox virus in 2022 highlights the potential threat it poses to public health. Due to the lack of specific treatments, the monkeypox virus I7L protease has been identified as a potential target for the development of new drugs. Through computational modeling and virtual screening, 14 potential inhibitors of the monkeypox I7L protease have been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Boqian Zhou, Yongguang Zhang, Wanyun Jiang, Haiyang Zhang
Summary: This study used computational methods to perform virtual screening of FDA-approved drugs and identified potential inhibitors against ALDH2. Some compounds showed a low toxicity and comparable or stronger binding strength than known potent inhibitors. However, further verification is needed to confirm the efficacy of these compounds.
Review
Biochemistry & Molecular Biology
Beatriz Suay-Garcia, Jose I. Bueso-Bordils, Antonio Falco, Gerardo M. Anton-Fos, Pedro A. Aleman-Lopez
Summary: Traditionally, drug development involved time-consuming and costly processes, but the application of virtual combinatorial chemistry and virtual screening can greatly accelerate the search and development of drugs, while saving costs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Xinbo Yang, Xianrong Xing, Yirui Liu, Yuanjie Zheng
Summary: This study proposes a virtual drug screening method based on the M-pro structure to identify potential therapeutic drugs for COVID-19. Five compounds were found to have potential inhibitory effects on the SARS-CoV-2 M-pro, and further experimental verification was carried out.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Irini Doytchinova
Summary: Drug design is a complex pharmaceutical science that has transformed into a coherent and well-organized discipline with solid theoretical foundations. Its goal is to discover effective, specific, non-toxic, safe, and well-tolerated drugs. It is one of the most rapidly developing modern sciences, with advancements driven by the application of artificial intelligence.
Article
Chemistry, Medicinal
Nermin Eissa, Karthikkumar Venkatachalam, Petrilla Jayaprakash, Priya Yuvaraju, Markus Falkenstein, Holger Stark, Bassem Sadek
Summary: The study demonstrates the significant mitigating effects of a multiple-active H3R/D2R/D3R antagonist on social deficits related to ASD.
Article
Biochemistry & Molecular Biology
Leonie Beyer, Aylin Sara Kabatas, Susanne Mommert, Holger Stark, Thomas Werfel, Ralf Gutzmer, Katrin Schaper-Gerhardt
Summary: Histamine plays a crucial role in upregulating the IL-18/IL-18R axis and activating human eosinophils from atopic dermatitis patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cecilia M. S. Q. Aranha, David Reiner-Link, Luisa R. Leitzbach, Flavia B. Lopes, Holger Stark, Joao Paulo S. Fernandes
Summary: A series of 21 substituted aryl-alkyl-piperazines were designed, prepared, and tested for their binding affinities at histamine H3 and dopamine D3 receptors, as well as acetyl- and butyrylcholinesterases, in order to generate a potential treatment profile for cognitive impairment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Ozge Uluckan, Sandro Bruno, Yichen Wang, Nathalie Wack, Jenny Wilzopolski, Jean-Francois Goetschy, Corinne Delucis-Bronn, Beatrice Urban, Dominique Fehlmann, Holger Stark, Alice Hauchard, Elsa Roussel, Dominique Kempf, Klemens Kaupmann, Friedrich Raulf, Wolfgang Baeumer, Till A. Rohn, Hans Gunter Zerwes
Summary: In this study, we investigated the pharmacology of adriforant in primary murine cells and in vivo models. Our results showed that adriforant functions as a competitive antagonist of murine histamine receptor 4, reducing itch and inflammation in mice. However, the clinical trial with adriforant did not demonstrate efficacy, suggesting that targeting histamine receptor 4 alone may not be sufficient to treat AD patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nermin Eissa, Mohamed Al Awad, Shilu Deepa Thomas, Karthikkumar Venkatachalam, Petrilla Jayaprakash, Sicheng Zhong, Holger Stark, Bassem Sadek
Summary: Dysregulation in neurotransmitters and the MAPK pathway is associated with neuropsychiatric disorders like autism spectrum disorder (ASD). Chronic administration of the antagonist ST-713 at the H3R and D2/D3R reduced repetitive self-grooming and aggression in BTBR mice. These effects were reversed by co-administration of H3R agonist or anticholinergic drug. ST-713 also suppressed MAPK pathway proteins and proinflammatory markers, while increasing histamine and dopamine levels in hippocampal tissue. These findings suggest the potential of multiple-targeting compounds like ST-713 in neurodevelopmental disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Matthias Hennemann, Timothy Clark
Summary: A modified neglect of differential overlap theory was used to parameterize water and its oligomers, with the addition of polarization functions, Feynman dispersion, and a slight modification of hydrogen nucleus treatment. The results demonstrated the feasibility of obtaining accurate geometries and energies for hydrogen-bonded water aggregates.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Justyna Godyn, Paula Zareba, Dorota Stary, Maria Kaleta, Kamil J. Kuder, Gniewomir Latacz, Szczepan Mogilski, David Reiner-Link, Annika Frank, Agata Doroz-Plonka, Agnieszka Olejarz-Maciej, Sylwia Sudol-Talaj, Tobias Nolte, Jadwiga Handzlik, Holger Stark, Anna Wieckowska, Barbara Malawska, Katarzyna Kiec-Kononowicz, Dorota Lazewska, Marek Bajda
Summary: The study designed and synthesized a novel series of benzophenone derivatives. Among them, compound 6 showed high affinity for H3R and significant inhibitory activity towards BuChE. In vitro studies demonstrated that compound 6 had moderate metabolic stability and good permeability. In vivo activity tests revealed that compound 6 exhibited analgesic properties in acute and inflammatory pain.
Article
Cell Biology
Kerstin Griess, Michael Rieck, Nadine Muller, Gergely Karsai, Sonja Hartwig, Angela Pelligra, Robert Hardt, Caroline Schlegel, Jennifer Kuboth, Celina Uhlemeyer, Sandra Trenkamp, Kay Jeruschke, Jurgen Weiss, Leon Peifer-Weiss, Weiwei Xu, Sandra Cames, Xiaoyan Yi, Miriam Cnop, Mathias Beller, Holger Stark, Arun Kumar Kondadi, Andreas S. Reichert, Daniel Markgraf, Marianne Wammers, Dieter Haeussinger, Oliver Kuss, Stefan Lehr, Decio Eizirik, Heiko Lickert, Eckhard Lammert, Michael Roden, Dominic Winter, Hadi Al-Hasani, Doris Hoeglinger, Thorsten Hornemann, Jens C. Bruning, Bengt-Frederik Belgardt
Summary: Impaired proinsulin-to-insulin processing in pancreatic beta-cells is a key defective step in both type 1 diabetes and type 2 diabetes. This study reveals the roles of specific sphingolipid species and sphingolipid-binding proteins in beta-cell function and T2D-associated beta-cell failure.
NATURE CELL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Jacqueline C. Calderon, Passainte Ibrahim, Dorothea Gobbo, Francesco Luigi Gervasio, Timothy Clark
Summary: We propose a metadynamics protocol to characterize the activation free-energy profiles of G-protein coupled receptors, focusing on the 5HT1A-receptor as a proof-of-principle study. By using the A100 activation index based on inter-helix distances, we perform metadynamics simulations and obtain free-energy profiles for the receptor in various complexes. Our results not only agree with previous experimental and computational data, but also provide detailed insights into the differences between active and inactive conformations and the role of microswitches in the activation mechanism.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Donia E. Hafez, Mariam Dubiel, Gabriella La Spada, Marco Catto, David Reiner-Link, Yu-Ting Syu, Mohammad Abdel-Halim, Tsong-Long Hwang, Holger Stark, Ashraf H. Abadi
Summary: Introduced a multi-targeted ligand for neurodegenerative diseases, such as Alzheimer's disease, which offers an improved therapeutic alternative compared to the traditional one-target, one-molecule approach. Certain compounds showed potential for multi-targeting by evaluating their interactions with AChE, BuChE, and MAO-B, suggesting their potential as lead structures for developing new multi-targeting anti-AD agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Henrik Gotfredsen, Dominik Thiel, Phillip M. Greibel, Lan Chen, Marcel Krug, Ilias Papadopoulos, Michael J. Ferguson, Mogens Brondsted Nielsen, Tomas Torres, Timothy Clark, Dirk M. Guldi, Rik R. Tykwinski
Summary: This study investigates the influence of sensitizer-chromophore geometry on the separation of singlet excited states into triplet excited states. Two conjugates with different arrangements were synthesized and compared. The results show that the energy transfer rate is 26 times faster in the peripheral arrangement, even though the chromophores are farther apart. This rate acceleration is attributed to the more favorable relative orientation of the transition dipole moments in the peripheral structure. These findings are of significant importance for solar energy research.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Dorota Lazewska, Maria Kaleta, Paula Zareba, Justyna Godyn, Mariam Dubiel, Ewelina Honkisz-Orzechowska, Agata Doroz-Plonka, Anna Wieckowska, Holger Stark, Katarzyna Kiec-Kononowicz
Summary: The aim of the study was to find new multitargeting ligands. Acetyl- and propionyl-phenoxy-pentyl(-hexyl) derivatives were designed and tested for their affinity to human H(3) receptors, inhibition of cholinesterases and monoamine oxidase B, as well as cell toxicity. Compounds 16 and 17 showed promising results with high affinity for H(3) receptors, good inhibition of cholinesterases, and no cell toxicity up to 50 μM.
Article
Chemistry, Multidisciplinary
Yifan Bo, Yuxuan Hou, Dominik Thiel, Renee Weiss, Timothy Clark, Michael J. Ferguson, Rik R. Tykwinski, Dirk M. Guldi
Summary: This study designs two tetracene dimers with different linking modes, and characterizes the interplay between intramolecular singlet fission (intra-SF) and intramolecular triplet-triplet annihilation up-conversion (intra-TTA-UC) through steady-state and time-resolved absorption and fluorescence spectroscopy. By using Pd-phthalocyanine as a sensitizer, intra-TTA-UC is achieved in the two dimers via indirect photoexcitation in the near-infrared part of the solar spectrum. Temperature-dependent measurements reveal the impact of thermal effects on intra-SF and intra-TTA-UC in different dimers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Jacqueline C. Calderon, Alberto Herrera, Frank W. Heinemann, Jens Langer, Anthony Linden, Ahmed Chelouan, Alexander Grasruck, Rafael Anez, Timothy Clark, Romano Dorta
Summary: The inversion barriers Delta G double dagger for planar chiral phosphine-alkene and sulfonamide-alkene hybrid ligands based on phenyl-dibenz-[b,f]-azepine have been determined by density-functional theory calculations. Analysis of the structural and electronic characteristics of the minima and transition states explains the magnitudes of Delta G double dagger and the geometrical changes during the inversion process. The steric repulsion caused by bulky substituents attached to the azepine nitrogen atom has a pronounced effect on the Delta G double dagger value, explaining the stereochemical stability of the ligands.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wiebke Zika, Andreas Hirsch, Rene Weiss, Simone Pinter, Christoph M. Schuesslbauer, Timothy Clark, Andreas Hirsch, Dirk M. Guldi
Summary: This study investigates the interconversion between QC and NBD and their application in energy storage through photo-assays. An oxidative electron transfer is observed during the QC-to-NBD isomerization using transient absorption spectroscopy. The complementary use of time-resolved and steady-state spectroscopies allows for a complete description of the photoisomerization reaction of NBDs.