Article
Chemistry, Multidisciplinary
Shizhen Zhao, Xinping Li, Wenjing Peng, Le Wang, Wenling Ye, Yang Zhao, Wenbo Yin, Wei-Dong Chen, Weiguo Li, Yan-Dong Wang
Summary: TGR5 is an emerging target for anti-diabetic drug development, and in this study, common feature pharmacophore models and molecular docking were used to identify novel nonsteroidal TGR5 agonists. Among the 20 compounds screened, V12 and V14 showed promising TGR5 agonistic activity with EC50 values of 19.5 mu M and 7.7 mu M, respectively. These compounds could be potential candidates for TGR5 agonists development.
Article
Biochemistry & Molecular Biology
Mohd Imran Khan, Taehwan Park, Mohammad Azhar Imran, Venu Venkatarame Gowda Saralamma, Duk Chul Lee, Jaehyuk Choi, Mohammad Hassan Baig, Jae-June Dong
Summary: Heat shock protein 90 (Hsp90) is a crucial molecular chaperone in cancer development, and the identification of potential Hsp90 inhibitors using machine learning and in silico approaches has shown promising inhibitory activity on cancer cell lines.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
P. M. Gurubasavaraja Swamy, Nahid Abbas, Prasad Sanjay Dhiwar, Ekta Singh, Abhishek Ghara, Arka Das
Summary: In this study, a 3D QSAR pharmacophore model was generated using substituted pyrimidine class of Aurora-A kinase inhibitors, revealing the crucial role of molecular features in inhibitory activity. Five potential compounds were identified through screening and docking, demonstrating their distinctive ability to inhibit Aurora-A kinase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Lamees Hegazy, Lauren E. Gill, Kelly D. Pyles, Christopher Kaiho, Sophia Kchouk, Brian N. Finck, Kyle S. McCommis, Bahaa Elgendy
Summary: This study reveals the structure-function relationships of the mitochondrial pyruvate carrier (MPC) complex using homology modeling and mutagenesis experiments. Based on this, a pharmacophore model is developed and a virtual screen identifies five new drug-like MPC inhibitors.
Article
Chemistry, Physical
Arman Safavi, Elaheh Sadat Ghodousi, Mehdi Ghavamizadeh, Mohamad Sabaghan, Omid Azadbakht, Ali Veisi, Hossein Babaei, Zahra Nazeri, Mehrnaz Karimi Darabi, Vahid Zarezade
Summary: FTase is considered an effective target in treating cancer, and a 3D-QSAR pharmacophore search was conducted to identify potential inhibitors. The pharmacophore models were validated and evaluated, leading to the selection of two compounds for further Molecular Dynamics studies to investigate their inhibitory effects on FTase.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Alireza Mohebbi
Summary: This study aimed to discover stable SMO inhibitors for both wild-type and mutant SMOs using a validated 12-feature pharmacophore model and virtual screening. One lead compound, LCT10312, showed high affinity to SMO and caused significant conformational changes in the SMO structure upon binding. Molecular dynamic simulation revealed stable interaction of LCT10312 with SMO and large atom motions, indicating SMO structural fluctuation. The lead compound also showed high predicted binding scores to several clinically relevant SMO mutants.
JOURNAL OF MOLECULAR MODELING
(2023)
Review
Pharmacology & Pharmacy
Ratul Bhowmik, Ajay Manaithiya, Bharti Vyas, Ranajit Nath, Kamal A. Qureshi, Seppo Parkkila, Ashok Aspatwar
Summary: This article discusses various techniques used in tuberculosis drug discovery, including computational approaches. It introduces different databases, methods, approaches, and software used in conducting QSAR, pharmacophore modeling, and molecular docking. The important molecules discovered using these computational approaches and drugs in clinical trials for tuberculosis are also discussed. Finally, the challenges and future perspectives of these techniques in drug discovery are summarized.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Lianxiang Luo, Ai Zhong, Qu Wang, Tongyu Zheng
Summary: In this study, marine natural compound 51320 was identified as a small molecule inhibitor of PD-L1 through various screening methods.
Article
Biochemistry & Molecular Biology
Samo Guzelj, Tihomir Tomasic, Ziga Jakopin
Summary: A hybrid docking and pharmacophore modeling approach was used to identify key interactions between NOD2 ligands and residues in the putative ligand-binding site. Two NOD2 antagonist compounds were identified as hits and represent valuable starting points for future optimization.
Article
Biochemistry & Molecular Biology
Xiaojiao Zheng, Chenchen Wang, Na Zhai, Xiaogang Luo, Genyan Liu, Xiulian Ju
Summary: The study investigated a novel series of imidazo[1,2-a]-pyridine derivatives for their binding modes in the GABA(A) receptor binding pocket using various methods. The results provide important information for the development of novel drugs with antipsychotic activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chao Zhang, Junjie Xiang, Qian Xie, Jing Zhao, Hong Zhang, Erfang Huang, Pangchui Shaw, Xiaoping Liu, Chun Hu
Summary: The study reveals the potential of PA(N) in contributing to host protein shutdown during influenza A infection. Inhibition of viral RdRP's endonuclease activity is seen as a promising avenue for novel antiviral therapy. By developing a ligand-based pharmacophore model, structurally diverse compounds with better efficacy as PA(N) endonuclease inhibitors can be envisaged.
Article
Biochemistry & Molecular Biology
Bhumi M. Shah, Palmi Modi, Priti Trivedi
Summary: Pharmacophore modeling, molecular docking, and in silico ADME studies were conducted to determine the binding mode and drug likeliness profile of Pyrrolidine derivatives as Dipeptidyl peptidase IV inhibitors. A statistically significant 3D-QSAR model was generated, with high correlation and predictive capability, indicating potential for novel drug design.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Immunology
Vikas Kumar, Shraddha Parate, Danishuddin, Amir Zeb, Pooja Singh, Gihwan Lee, Tae Sung Jung, Keun Woo Lee, Min Woo Ha
Summary: This study aimed to identify potential inhibitors against SYK with higher affinity, selectivity, and drug-like properties compared to existing inhibitors. Through the use of 3D-QSAR modeling, molecular docking, and molecular dynamics simulations, multiple potential inhibitors were screened and their binding modes were analyzed. The study found that these compounds formed important interactions with key residues of SYK.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Genshen Zhong, Yichun Wang, Qi Wang, Minna Wu, Yichuang Liu, Shitao Sun, Zhenli Li, Jinle Hao, Peiyuan Dou, Bin Lin
Summary: The study focused on a new compound AK-778-XXMU, which showed potential as a therapeutic agent against glioma by inhibiting the ID2 protein. The compound demonstrated significant suppression of the viability of glioma cells through targeting ID2, suggesting it may serve as a potent ID2 antagonist for glioma treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shanshan Y. C. Bradford, Lea El Khoury, Yunhui Ge, Meghan Osato, David L. Mobley, Marcus Fischer
Summary: By systematically investigating protein conformational changes in response to temperature and ligand binding, new global and local structural changes were revealed in the T4 lysozyme L99A cavity when shifting to room temperature. Temperature-induced alterations in protein and ligand structures can influence computational methods and the utility of structural information in ligand binding predictions, highlighting the potential limitations of relying solely on cryogenic data for computational purposes.
Article
Oncology
Mona Kafka, Fabian Mayr, Veronika Temml, Gabriele Moeller, Jerzy Adamski, Julia Hofer, Stefan Schwaiger, Isabel Heidegger, Barbara Matuszczak, Daniela Schuster, Helmut Klocker, Jasmin Bektic, Hermann Stuppner, Iris E. Eder
Article
Chemistry, Medicinal
Chau Phi Dinh, Alexia Ville, Konstantin Neukirch, Guillaume Viault, Veronika Temml, Andreas Koeberle, Oliver Werz, Daniela Schuster, Hermann Stuppner, Pascal Richomme, Jean-Jacques Helesbeux, Denis Seraphin
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Fabian Mayr, Gabriele Moeller, Ulrike Garscha, Jana Fischer, Patricia Rodriguez Castano, Silvia G. Inderbinen, Veronika Temml, Birgit Waltenberger, Stefan Schwaiger, Rolf W. Hartmann, Christian Gege, Stefan Martens, Alex Odermatt, Amit V. Pandey, Oliver Werz, Jerzy Adamski, Hermann Stuppner, Daniela Schuster
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Medicinal
Alexandra K. Knox, Christina Kalchschmid, Daniela Schuster, Francesca Gaggia, Ronald Gust
Summary: The compound GW7604, a derivative of (Z)-4-hydroxy-tamoxifen, was linked to molecules that bind to the coactivator binding site, resulting in an optimized pharmacological profile. Thioxo-quinazolinone derivative 16 showed high affinity to estrogen receptor beta and acted as a pure estradiol antagonist, demonstrating selective ER degradation/downregulation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Konstantin Neukirch, Khaled Alsabil, Chau-Phi Dinh, Rossella Bilancia, Martin Raasch, Alexia Ville, Ida Cerqua, Guillaume Viault, Dimitri Breard, Simona Pace, Veronika Temml, Elena Brunner, Paul M. Jordan, Marta C. Marques, Konstantin Loeser, Andre Gollowitzer, Stephan Permann, Jana Gerstmeier, Stefan Lorkowski, Hermann Stuppner, Ulrike Garscha, Tiago Rodrigues, Goncalo J. L. Bernardes, Daniela Schuster, Denis Seraphin, Pascal Richomme, Antonietta Rossi, Alexander S. Mosig, Fiorentina Roviezzo, Oliver Werz, Jean-Jacques Helesbeux, Andreas Koeberle
Summary: Compound 27a, inspired by endogenous LCMs, shows potent anti-inflammatory effects in human immune cells and animal models, with superior metabolic stability compared to LCMs. The study highlights 27a as an orally active drug candidate that limits inflammation with greater potency than endogenous leads.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Christian Kretzer, Paul M. Jordan, Katharina P. L. Meyer, Daniel Hoff, Markus Werner, Robert Klaus Hofstetter, Andreas Koeberle, Antonio Cala Peralta, Guillaume Viault, Denis Seraphin, Pascal Richomme, Jean-Jacques Helesbeux, Hermann Stuppner, Veronika Temml, Daniela Schuster, Oliver Werz
Summary: Specialized pro-resolving mediators (SPMs) are lipid mediators (LMs) produced from polyunsaturated fatty acids (PUFAs) and have anti-inflammatory and inflammation-resolving properties. This study found that a natural chalcone from Melodorum fruticosum can modulate LM biosynthesis in human macrophages by suppressing pro-inflammatory leukotrienes and stimulating the formation of SPMs.
BIOCHEMICAL PHARMACOLOGY
(2022)
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
Navista Sri Octa Ujiantari, Seungmin Ham, Chisae Nagiri, Wataru Shihoya, Osamu Nureki, Dana Sabine Hutchinson, Daniela Schuster
Summary: This study utilized virtual screening and in vitro assays to confirm the biological activity of predicted β(3)-AR agonists. Several compounds showed activity against both human and mouse β(3)-AR.
MOLECULAR INFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Gabriele Moeller, Veronika Temml, Antonio Cala Peralta, Oceane Gruet, Pascal Richomme, Denis Seraphin, Guillaume Viault, Luisa Kraus, Petra Huber-Cantonati, Elisabeth Schopfhauser, Johanna Pachmayr, Janina Tokarz, Daniela Schuster, Jean-Jacques Helesbeux, Kenneth Allen Dyar
Summary: Naturally occurring substances, such as chalcones, have been found to inhibit AKR1C3 and show potential as antiproliferative agents against prostate cancer. This study aims to analyze the structure-activity relationships of 12 synthesized chalcones and identify favorable substitutions for AKR1C3 inhibition. The results suggest that certain modifications increase the inhibitory activity of chalcones, paving the way for further development of compounds with improved AKR1C3 inhibitory activity.
Article
Plant Sciences
Adriana Trifan, Andra-Cristina Bostanaru, Simon Vlad Luca, Veronika Temml, Muhammad Akram, Sonja Herdlinger, Lukasz Kulinowski, Krystyna Skalicka-Wozniak, Sebastian Granica, Monika E. Czerwinska, Aleksandra Kruk, Helene Greige-Gerges, Mihai Mares, Daniela Schuster
Summary: This study found that honokiol and magnolol have high activity against dermatophyte infections, acting as fungicidal agents through inhibition of ergosterol biosynthesis. Synergistic effects were observed when magnolol was combined with terbinafine, while honokiol only showed additive effects. Additionally, magnolol displayed inhibitory effects on pro-inflammatory cytokines released by stimulated human neutrophils.
Article
Biochemistry & Molecular Biology
Lukas Zell, Constanze Lainer, Jakub Kollar, Veronika Temml, Daniela Schuster
Summary: Diseases of the central nervous system are becoming more prevalent globally. The current drugs targeting D2R suffer from adverse effects due to promiscuous receptor activity. This study combines in silico and in vitro approaches to identify novel D2R ligands, which could aid in developing new drug candidates for D2R-associated pathologies.
Article
Biochemistry & Molecular Biology
Lisa Vieider, Eva Zoeller, Erik Romp, Martin Schoenthaler, Victor Hernandez-Olmos, Veronika Temml, Thomas Hasenoehrl, Daniela Schuster, Oliver Werz, Ulrike Garscha, Barbara Matuszczak
Summary: A series of derivatives of the potent dual sEH/FLAP inhibitor diflapolin were designed, synthesised, and evaluated. These compounds contain a benzimidazole subunit and were tested for their inhibitory activity against sEH and FLAP. Molecular modelling tools were used to analyse the structure-activity relationships on both targets and predict solubility and gastrointestinal absorption. The most promising inhibitors in this series are 5a, 6b, and 6c.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Veronika Temml, Jakub Kollar, Theresa Schoenleitner, Anna Hoell, Daniela Schuster, Zsofia Kutil
Summary: Virtual screening followed by in vitro testing was used to discover novel active compounds for Glutamate carboxypeptidase II (GCPII) inhibition. By creating structure- and ligand-based pharmacophore models, virtual screening of a compound library led to the identification of six hits with moderate to high inhibitory potency against GCPII. The best virtual hit, a modified xanthene, showed an IC50 value of 353 +/- 24 nM. These findings demonstrate the applicability of pharmacophore-based modeling in the discovery of GCPII-specific inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Lukas Zell, Alina Bretl, Veronika Temml, Daniela Schuster
Summary: Different dopamine receptor subtypes are involved in various conditions, and this study identified novel ligands with high affinity and selectivity for D2R/D3R. In vitro experiments and in silico analysis were used to rationalize the ligands' selectivity and interaction with secondary binding pockets. This research contributes to the understanding of structural motifs responsible for DR subtype selectivity and can aid drug development in D2R/D3R-associated pathologies.
Article
Chemistry, Medicinal
Veronika Temml, Jakub Kollar, Theresa Schoenleitner, Anna Hoell, Daniela Schuster, Zsofia Kutil
Summary: In this study, structure- and ligand-based pharmacophore models were used for virtual screening of the SPECS compound library to discover novel GCPII-specific inhibitors. Six hits with moderate to high inhibitory potency were found, and the best virtual hit, a modified xanthene, inhibited GCPII with an IC50 value of 353 +/- 24 nM. This research demonstrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemical Research Methods
K. Ramki, G. Thiruppathi, Selva Kumar Ramasamy, P. Sundararaj, P. Sakthivel
Summary: A chromone-based ratiometric fluorescent probe L2 was developed for the selective detection of Hg(II) in a semiaqueous solution. The probe exhibited enhanced fluorescence in its aggregated state and even higher fluorescence when chelated with Hg(II). The probe demonstrated high sensitivity and specificity for Hg(II) detection and was successfully applied for imaging Hg(II) in a living model.
Article
Biochemical Research Methods
Qun Zhang, Rui Yang, Gang Liu, Shiyan Jiang, Jiarui Wang, Juqiang Lin, Tingyin Wang, Jing Wang, Zufang Huang
Summary: This research aims to develop a cost-effective and portable method for measuring creatinine levels using the enhanced Tyndall effect phenomenon. The method offers a promising solution for monitoring renal healthcare in resource-limited settings.