Article
Chemistry, Multidisciplinary
Xiao Jia, Dominique Schols, Chris Meier
Summary: This article describes the synthesis of two types of nucleotide prodrugs containing different nucleoside analogs and their effective inhibition against HIV-2 replication. The prodrugs exhibited high stability and antiviral activity in cell extracts.
Article
Chemistry, Medicinal
Simon Weising, Stefan Weber, Dominique Schols, Chris Meier
Summary: The study describes a triphosphate prodrug of 3'-fluoro-3'-deoxythymidine (FLT) with the aim of bypassing phosphorylation steps, increasing selectivity and stability, for potential use in HIV treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiao Jia, Dominique Schols, Chris Meier
Summary: We synthesized and evaluated three different nucleotide prodrug systems. These prodrugs showed remarkable antiviral activity against HIV in infected cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Chenglong Zhao, Xiao Jia, Dominique Schols, Jan Balzarini, Chris Meier
Summary: This study presents the design of new nucleoside analogue derivatives with the aim of developing more effective anti-HIV drugs. These compounds were shown to be active against HIV in cell culture experiments, and the hydrolysis of the prodrug masks was investigated.
Article
Chemistry, Medicinal
Xiao Jia, Dominique Schols, Chris Meier
Summary: We synthesized and evaluated three different nucleotide prodrug systems and demonstrated their release in cell extracts and phosphate buffer saline. Several compounds showed extremely high activity against HIV-1/2 replication in HIV-infected cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yuqin Wang, Pingping Fan, Shanyu Zhang, Liying Wang, Xinyue Li, Wendong Jia, Yao Liu, Kefan Wang, Xiaoyu Du, Panke Zhang, Shuo Huang
Summary: In this study, a specially engineered nanopore sensor was used to successfully discriminate all canonical ribonucleoside mono-, di-, and triphosphates, and a machine-learning algorithm was developed with a general accuracy of 99.9% for ribonucleotide sensing. This sensing strategy was also applied to identify ribonucleotide components in different phosphorylated forms.
Article
Chemistry, Multidisciplinary
Guillaume Hoffmann, Madalen Le Gorrec, Emeline Mestdach, Stephen Cusack, Loic Salmon, Malene Ringkjobing Jensen, Andres Palencia
Summary: This study reveals a novel enzyme-independent prodrug activation mechanism by boron-based compounds targeting leucyl-tRNA synthetase. These benzoxaboroles act as prodrugs that activate their bioconversion by forming a specific and reversible inhibition adduct with ATP, AMP, or the terminal adenosine of the tRNALeu. This adenosine-dependent activation mechanism explains the good druglike properties and broad efficacy of benzoxaboroles against different human pathogens.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Zhao-Hui Wen, Meng-Meng Wang, Ling-Yun Li, Piet Herdewijn, Robert Snoeck, Graciela Andrei, Zhao-Peng Liu, Chao Liu
Summary: In this study, the synthesis of lipid prodrugs of beta-D-N4-hydroxycytidine (NHC) and a 3'-fluoro modified NHC analogue was reported, and their antiviral activity against five variants of SARS-CoV-2 was evaluated. The lipid prodrugs showed potent antiviral activity against the tested variants, with comparable or higher EC50 values than remdesivir and molnupiravir. The 3'-F analogue of NHC only exhibited minor antiviral activity against the Omicron variant, while no activity was observed against other variants. The promising antiviral data of the lipid prodrugs suggest their potential as new anti-SARS-CoV-2 drugs.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nazarii Sabat, Abdelhakim Ouarti, Evelyne Migianu-Griffoni, Marc Lecouvey, Olivier Ferraris, Florian Gallier, Christophe Peyrefitte, Nadege Lubin-Germain, Jacques Uziel
Summary: Phosphoramidates obtained using the ProTide strategy have been known to enhance the biological activity of nucleosides. In this study, a series of prodrugs of SRO-91 were synthesized and investigated for their antitumor and antiviral activities. Two compounds showed inhibitory effects on cell proliferation, while another compound exhibited antiviral activity against Crimean-Congo Hemorrhagic Fever virus.
BIOORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Kiran S. Toti, Nicole Pribut, Michael D'Erasmo, Madhuri Dasari, Savita K. Sharma, Perry W. Bartsch, Samantha L. Burton, Hannah B. Gold, Anatoliy Bushnev, Cynthia A. Derdeyn, Adriaan E. Basson, Dennis C. Liotta, Eric J. Miller
Summary: Nucleoside- and nucleotide-based therapeutics play crucial roles in treating malignant and viral diseases. Prodrugs, commonly used for improving bioavailability and efficacy, can be optimized with small adjustments to enhance pharmacokinetic profiles. In this study, the fine-tuning of lipid prodrugs of tenofovir, a nucleotide HIV reverse transcriptase inhibitor, successfully reduced liver omega-oxidation while maintaining potent antiviral activity. This research provides important insights into lipid prodrug strategies and the delivery of acyclic nucleoside phosphonates.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Applied
Sumei Ren, Mark A. Huffman, Aaron M. Whittaker, Hao Yang, Christopher C. Nawrat, David J. Waterhouse, Kevin M. Maloney, Neil A. Strotman
Summary: The synthesis of the carbon-14-labeled unnatural nucleoside islatravir, an investigational HIV drug, was achieved through a one-pot biocatalytic cascade starting from acetaldehyde-2-C-14. Combining enzymatic reactions into multistep biocatalytic cascades not only accelerates delivery and increases the yield, but also eliminates handling of radioactive intermediates and minimizes radioactive waste.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Sadia Abbas, Saira Afzal, Humaira Nadeem, Dilawar Hussain, Peter Langer, Jean Sevigny, Zaman Ashraf, Jamshed Iqbal
Summary: The importance of extracellular nucleotides is well recognized due to their role as ligands for P2X and P2Y receptors and their modulation of various biological functions. Ecto-nucleotidases, a chain of enzymes, are responsible for maintaining the extracellular concentration of these nucleotides. Nucleoside triphosphate diphosphohydrolases (NTPDases) are an important enzyme family that dephosphorylates these nucleotides. Overexpression of NTPDases can lead to pathological conditions such as cancer and thrombosis. Only a few NTPDase inhibitors have been reported, creating a scarcity in this area. Therefore, thiadiazole amide derivatives were synthesized and screened against human NTPDases to find potential inhibitors.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jirayu Kammarabutr, Panupong Mahalapbutr, Hisashi Okumura, Peter Wolschann, Thanyada Rungrotmongkol
Summary: This study indicates that certain anti-HIV drugs may have higher susceptibility against HBV-RT enzyme, potentially serving as a promising drug option for HBV-infected patients with 3TC resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Organic
Yuhua Huang, Frank Bennett, Alexei Buevich, Vinay Girijavallabhan, Angela D. Kerekes, Hsueh-Cheng Huang, Paul Tawa, Stephane L. Bogen, Ian W. Davies
Summary: This study describes the syntheses of 2'-amino-2'-ethynyl guanosine and uridine using an intramolecular aminohydroxylation reaction, followed by evaluation of their inhibitory activity against hepatitis C virus NS5B polymerase.
TETRAHEDRON LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Wen-juan Hu, Lu Chang, Ying Yang, Xin Wang, Yuan-chao Xie, Jing-shan Shen, Bo Tan, Jia Liu
Summary: In this study, the pharmacokinetics and tissue distributions of Remdesivir in mice were evaluated, showing different levels and metabolic stabilities of RDV and its metabolites in blood as well as high concentrations in lung, liver, and kidney.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Pharmacology & Pharmacy
Iwona E. Glowacka, Katarzyna Gawron, Dorota G. Piotrowska, Mirthe Graus, Graciela Andrei, Dominique Schols, Robert Snoeck, Anita Camps, Emiel Vanhulle, Kurt Vermeire
Summary: In this study, a series of 48 hybrids were synthesised and evaluated for antiviral activity. The hybrids contained a diethoxyphosphoryl group connected to the triazole moiety via ethylene or propylene linker, and substituted benzyl or benzoyl function in the quinazoline-2,4-dione moiety. The hybrids showed potent antiviral activities against Respiratory Syncytial Virus (RSV), with some weak activity against varicella zoster virus and human cytomegalovirus.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
Article
Chemistry, Organic
Neng Wang, Hang Wang, Lin-Xi Wan, Xiao-Huan Li, Xian-Li Zhou, Jia-Hong Li, Steven De Jonghe, Dominique Schols, Jin-Bu Xu, Feng Gao
Summary: The biorelevant sulfur-containing Euphorbia diterpenes with scarce 5/7/6/3 premyrsinane-and 5/7/6 myrsinanetype backbones were easily synthesized from naturally abundant lathyrane-type Euphorbia factor L3 by visible-light-triggered tandem thiol-ene click reaction/transannular cyclization and regioselective cyclopropane ring-opening. The universality of this synthesis route was confirmed by successfully obtaining the selenide diterpene. This concise synthesis strategy offers a mild and efficient method for obtaining structurally diverse Euphorbia diterpenes, including a promising anti-HIV bioactive premyrsinane diterpene 3h.
Article
Biochemistry & Molecular Biology
Max Van Hoof, Sandra Claes, Katrijn Boon, Tom Van Loy, Dominique Schols, Wim Dehaen, Steven De Jonghe
Summary: Upregulated CXCR2 signalling is common in inflammatory, autoimmune, neurodegenerative diseases, and cancer, making CXCR2 antagonism a promising therapeutic strategy. Previous research identified a pyrido[3,4-d]pyrimidine analogue as a potent CXCR2 antagonist. This study aims to improve the CXCR2 antagonistic potency through structural modifications, but most new analogues lacked CXCR2 antagonism except for a 6-furanyl-pyrido[3,4-d]pyrimidine analogue.
Article
Plant Sciences
Katarina Magdalenic, Ulrike Ronse, Steven De Jonghe, Leentje Persoons, Dominique Schols, Julie De Munck, Charlotte Grootaert, John Van Camp, Matthias D'hooghe
Summary: Curcumin, a natural product, has broad biological activities, including anticancer properties. However, it is poorly absorbed by the body and shows non-specific activity in biological assays. Recent research has led to the development of benzothiazepane-based molecules with promising biological and drug-like properties. In this study, 14 new compounds were synthesized and tested for their cytotoxicity against cancer cells, providing insights into the structure-activity relationships of this new class of compounds.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Merel Oeyen, Eef Meyen, Dominique Schols
Summary: Cell-based electrical impedance technology can be used to monitor the consequences of Zika virus infection and cell replication in real time without the use of labels or invasive methods, providing real-time data. This method can also be used for the evaluation and characterization of antiviral compounds.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Pharmacology & Pharmacy
Evelien Vanderlinden, Arnaud Boonen, Sam Noppen, Geert Schoofs, Maya Imbrechts, Nick Geukens, Robert Snoeck, Annelies Stevaert, Lieve Naesens, Graciela Andrei, Dominique Schols
Summary: PRO-2000, a sulfonated polyanionic compound, has anti-SARS-CoV-2 activity by blocking the entry pathway and inhibiting the binding of the S protein to its receptor. It can potentially inhibit a broad range of SARS-CoV-2 variants.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Physical
Papisetti Venkatesham, Dominique Schols, Leentje Persoons, Sandra Claes, Akanksha Ashok Sangolkar, Raju Chedupaka, Rajeswar Rao Vedula
Summary: A series of 1,2,4-triazolothiazoles were efficiently synthesized using a one-pot process in the presence of EtOH/DMF. The synthesized compounds showed high purity and confirmed structures through spectral analysis. Among them, two derivatives displayed inhibitory activity against both HIV-1 and HIV-2, while seven compounds showed selectivity towards HIV-2. Compound 5f exhibited promising activity against Zika virus. Molecular docking studies were also conducted for the most active compounds.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Xiao Jia, Dominique Schols, Chris Meier
Summary: This article describes the synthesis of two types of nucleotide prodrugs containing different nucleoside analogs and their effective inhibition against HIV-2 replication. The prodrugs exhibited high stability and antiviral activity in cell extracts.
Meeting Abstract
Cardiac & Cardiovascular Systems
J. Kaes, E. Vanhulle, L. Seldeslachts, C. Hooft, H. Beeckmans, X. Jin, P. Kerckhof, J. Van Slambrouck, D. Van Raemelonck, G. Vande Velde, L. Naesens, D. Schols, L. J. Ceulemans, R. Vos, K. Vertneire, B. M. Vanaudenaerde
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Chemistry, Multidisciplinary
Valeriya S. S. Bolshakova, Olga A. A. Kraevaya, Alexander S. S. Peregudov, Vitaliy Yu. Markov, Svetlana V. V. Kostyuk, Dominique Schols, Alexander F. F. Shestakov, Pavel A. A. Troshin
Summary: We report a new reaction between thiophene derivatives and fullerene derivatives, resulting in a family of C-60 fullerene compounds with three different types of functional aromatic addends attached to the carbon cage. The discovered reaction provides a pathway for the synthesis of novel C-60 fullerene derivatives with promising antioxidant and antiviral properties.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maria Karelou, Dionysis Kampasis, Amalia D. Kalampaliki, Leentje Persoons, Andreas Kraemer, Dominique Schols, Stefan Knapp, Steven De Jonghe, Ioannis K. Kostakis, Sotiris S. Nikolaropoulos
Summary: Sixteen new 2-substituted quinazolines were synthesized and evaluated for their anti-proliferative activity against multiple cancer cell lines. Compound 17 showed remarkable activity against the majority of tested cell lines.
Article
Chemistry, Multidisciplinary
Jin-Bu Xu, Peng Wen, Neng Wang, Xiaohuan Li, Jia-Hong Li, Steven De Jonghe, Dominique Schols, Feng-Zheng Chen, Feng Gao
Summary: The rare Euphorbia glucoside E (1) was efficiently synthesized from the abundant lathyrane-type Euphorbia factor L(1) using a visible-light-induced tandem reaction with Sc(OTf)3 catalyst. Eupholathones 2 and 3 were also obtained by changing the reaction solvent. This method provides a convenient approach for constructing the scarce Euphorbia glucosides from lathyrane-type Euphorbia diterpenes and confirms their biogenetic relationship from a chemical perspective. Notably, compound 1 exhibited significant anti-HIV activity.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Xiao Jia, Dominique Schols, Chris Meier
Summary: We synthesized and evaluated three different nucleotide prodrug systems and demonstrated their release in cell extracts and phosphate buffer saline. Several compounds showed extremely high activity against HIV-1/2 replication in HIV-infected cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
