Article
Biotechnology & Applied Microbiology
Wei Liu, Shan Yuan, Miaomiao Jin, Mo Xian
Summary: Fluorine is an essential element in medicine, agriculture, and materials design, as it can enhance the functionality and performance of organic compounds. However, fluorine is rarely found in natural metabolism. Researchers have developed a new biosynthetic strategy to expand the molecular space by synthesizing 2-fluoro-3-hydroxypropionic acid (2-F-3-HP). This biocatalytic method offers significant advantages in terms of environmental and safety impacts.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Organic
Rongyao Li, Jing Zhang, Manman Sun, Jinjing Xu, Guo-Bo Huang, Jianbo Yan, Jianguo Yang, Zhiming Wang, Chao Ma
Summary: A TFA-catalyzed dehydrofluorinative cyclization of 2,2-difluoro-3-hydroxy-1,4-diketones has been developed in the presence of amines under mild conditions using readily prepared difluorinated substrates according to our reported literature. This protocol allows for rapid construction of fluoro 3(2H)-furanones with good to excellent yields and demonstrates good functional group tolerance. The easy scale-up synthesis also provides practical advantages.
Article
Biochemistry & Molecular Biology
Martin Holan, Kathryn Tucker, Natalia Dyatkina, Hong Liu, April Kinkade, Guangyi Wang, Zhinan Jin, Marija Prhavc
Summary: Nucleoside analogues have shown excellent efficacy as anti-HBV drugs, but long-term administration may lead to drug resistance. Thus, it is of high importance to search for nucleosides with novel scaffolds.
Article
Chemistry, Organic
Thazha P. Prakash, Jinghua Yu, Guillermo Vasquez, Charels R. Allerson, Eric E. Swayze
Summary: In this study, we report a convenient and scalable synthetic approach for the synthesis of 3'-fluoro hexitol adenosine and guanosine nucleoside analogues. The strategy used in this synthesis provides a concise and scalable method for the production of 3'-fluoro hexitol purine nucleosides, which can be used in genetic medicine development and diagnostic applications.
Article
Chemistry, Organic
Shaista Tahir, Jonas F. Wunsch, Matthias Rudolph, Frank Rominger, A. Stephen K. Hashmi
Summary: A convenient method using easily synthesizable alkynyl phosphonates to prepare strained phosphonate-substituted oxetan-3-ones is presented. By generating an alpha-oxo carbene species with the aid of a pyridine-N-oxide in a gold-catalyzed step, useful HWE reagents can be attained for organic synthesis, resulting in high yields of 2-alkenyl oxetan-3-one scaffold.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Erich F. Altenhofer, Michael J. Lawler, Pankaj Kumar, Leo A. Joyce, Matthew Fowler-Watters, Tao Pei, Zhen Li
Summary: The inherent instability of oligonucleotides in vivo poses a challenge for RNAi therapeutics development, but chemical modification to the 5'-terminus can enhance stability. Recent studies have shown that installing a 5'-cyclopropyl phosphonate at the terminus of an oligonucleotide can increase knockdown of targeted proteins. This paper presents the synthesis of a 5'-modified uridine.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Jingjing Sang, Li Feng, Rui Hu, Jichao Chen, Dandan Shang, Qing Bao, Weidong Rao
Summary: This study presents an unprecedented Sc(OTf)(3)-catalyzed C2-selective cyanation/defluorination cascade, which provides a novel and practical strategy for the synthesis of structurally diverse 3-(2-cyano)-indolyl substituted gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes. The obtained gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes can be easily transformed into 3-fluoro(perfluoroalkyl)-beta-carbolines with excellent efficiency under mild reaction conditions.
Review
Chemistry, Multidisciplinary
Amandine Pons, Laetitia Delion, Thomas Poisson, Andre B. Charette, Philippe Jubault
Summary: Fluorine-containing cyclopropanes are a subclass of cyclopropane derivatives with significant medicinal chemistry interest. Replacing a cyclopropane C-H or C-CH3 bond with fluorine can enhance biological activity and metabolic profile. This account discusses the development of new synthetic routes for fluoro-, difluoromethyl-, or trifluoromethyl-cyclopropanes, focusing on optimizing reaction efficiency and substrate selection.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Yong-Jin Wu, Gerard J. Porter, David B. Frennesson, Mark G. Saulnier
Summary: In this study, we have successfully synthesized two unique halopyridine isomers using simple synthetic methods, providing ideal functional groups for further chemical manipulations.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Rahimeh Hajinasiri
Summary: Phosphorus atom is crucial in various biological and natural compounds. Among them, phosphonates are highly sought after due to their antifungal, antibacterial, antimicrobial properties and their efficacy as haptens, catalytic antibodies, and enzyme inhibitors. Different materials such as Seyferth-Gilbert reagent (SGR), Bestmann-Ohira Reagent (BOR), phosphites, N-heterocyclic phosphine (NHP)-thioureas, alkynylphosphonates, and beta-keto phosphonates are widely used in the synthesis of phosphonates. Phosphonates are often synthesized through reactions such as phospha-Michael. This article reviews the latest methods for synthesizing various phosphonates, highlighting their importance.
Article
Chemistry, Multidisciplinary
Bruno Mattia Bizzarri, Angelica Fanelli, Lorenzo Botta, Marta De Angelis, Anna Teresa Palamara, Lucia Nencioni, Raffaele Saladino
Summary: Highly active amino imidazole carbonitrile derivatives decorated with alpha-amino acid side-chains were synthesized using a multicomponent microwave assisted reaction inspired by prebiotic chemistry. These compounds were used as annulation synthons for the preparation of novel heterocycles that showed significant antiviral activity against influenza A virus. This demonstrates the potential of prebiotic chemistry in generating chemical diversity for the discovery of new antiviral agents.
Article
Biochemistry & Molecular Biology
Iwona E. Glowacka, Anna Hartwich, Iwona Rozpara, Dorota G. Piotrowska
Summary: Efficient syntheses of functionalized (pyrrolidin-2-yl)phosphonate and (5-oxopyrrolidin-2-yl)phosphonate have been developed, involving 1,3-dipolar cycloaddition reactions. The stereochemistry of the synthesized compounds was established through conformational analysis and observed diagnostic signals.
Article
Chemistry, Inorganic & Nuclear
Max Rautenberg, Biswajit Bhattacharya, Chayanika Das, Franziska Emmerling
Summary: This study reported the synthesis and proton conductivity of three new mixed-ligand phosphonate-based MOFs. These MOFs have stable structures and high proton conductivity, showing potential applications in proton-exchange membrane fuel cells.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Chong Liu, Qi Chen, Stewart W. Schneller
Summary: To expand the antiviral properties of 2- and 3-fluoro-3-deazaneplanocins, researchers explored the potential of 2-(11) and 3-fluoro-1',6'-iso-3-deazaneplanocin A (12) in the evolving 3-deaza-1',6'-iso-neplanocin library. Compound 12 exhibited significant activity against H1N1, hepatitis B virus, norovirus, Ebola, and Marburg, with low toxicity. However, compound 11 showed limited antiviral effects and high toxicity, limiting its further usefulness.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Leixia Chu, Xiaoxia Luo, Taoting Zhu, Yingying Cao, Lili Zhang, Zixin Deng, Jiangtao Gao
Summary: In this study, the authors report the bioproduction of aminomethylphosphonate (AMP) and a chemical process for converting AMP to glyphosate. This research provides a green alternative in the production of glyphosate, a widely used herbicide.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Az-Eddine El Mansouri, Saida Lachhab, Ali Oubella, Mehdi Ahmad, Johan Neyts, Dirk Jochmans, Winston Chiu, Laura Vangeel, Steven De Jonghe, Hamid Morjani, Mustapha Ait Ali, Mohamed Zahouily, Yogesh S. Sanghvi, Hassan B. Lazrek
Summary: Analogous to pyrimidine and 1,3,4-oxadiazole, the newly synthesized pyrimidine-1,3,4-oxadiazole conjugated hybrid molecules exhibited potential anticancer activity. Specifically, compound 5e demonstrated significant growth inhibition against various cancer cell lines and induced apoptosis through caspase activation and cell-cycle arrest.
JOURNAL OF MOLECULAR STRUCTURE
(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
Biochemistry & Molecular Biology
Hui Yang, Elena Eremeeva, Mikhail Abramov, Maarten Jacquemyn, Elisabetta Groaz, Dirk Daelemans, Piet Herdewijn
Summary: An enzymatic method was developed to generate partially base-modified RNA constructs, as well as fully modified RNA constructs featuring multiple modified bases. The efficiency of the fully modified RNA constructs was enhanced by using different T7 RNA polymerase variants. The study also demonstrated the successful incorporation of modified bases into PCR products and the effectiveness of the modified RNA constructs in CRISPR-Cas9 cleavage assays.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Cecile Gasse, Puneet Srivastava, Guy Schepers, Joachim Jose, Marcel Hollenstein, Philippe Marliere, Piet Herdewijn
Summary: Chemical cell surface modification is an important field with great potential in tissue engineering, cell-based immunotherapy, and regenerative medicine. However, research on engineering bacterial tissues through chemical cell surface modification is lacking, especially in finding suitable molecular handles. In this study, a novel strategy using orthogonal nucleic acid-protein conjugation was developed to induce artificial bacterial aggregation. This system combines the selective and stable linkage of a protein Tag at the cell surface with the modularity and reversibility of aggregation through oligonucleotide hybridization. The immobilization of XNA via covalent, SNAP-tag-mediated interactions on cell surfaces for bacterial aggregation is reported for the first time.
Article
Chemistry, Medicinal
Max Van Hoof, Sandra Claes, Matic Proj, Tom Van Loy, Dominique Schols, Stanislav Gobec, Wim Dehaen, Steven De Jonghe
Summary: CCR7 signaling is important in immune cell and cancer cell migration, chronic inflammatory disorders, and lymph node metastases. However, there is currently a lack of potent and selective small molecule CCR7 antagonists. In this study, a triazolo[4,5-d]pyrimidine analogue was discovered as a potential CCR7 antagonist through screening. Structural optimization of this analogue resulted in improved potency and selectivity, with one derivative showing the most promising activity against CCR7 and CXCR2. Molecular docking studies confirmed the binding mode of these derivatives in CCR7 and CXCR2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Biochemistry & Molecular Biology
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Tom Vermeyen, Aliou M. Balde, Wouter A. Herrebout, Johan Neyts, Christophe Pannecouque, Luc Pieters, Emmy Tuenter
Summary: This study investigated the bioactive constituents of Hymenocallis littoralis and identified three previously undescribed compounds, as well as six known compounds. Some of these compounds showed weak inhibitory activity against SARS-CoV-2 at non-cytotoxic concentrations. Furthermore, a preliminary structure-activity relationship for lycorine-type alkaloids in anti-SARS-CoV-2 activity was explored, suggesting the importance of ring C.
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
Biochemistry & Molecular Biology
Pradeep S. Pallan, Terry P. Lybrand, Eriks Rozners, Mikhail Abramov, Guy Schepers, Elena Eremeeva, Piet Herdewijn, Martin Egli
Summary: Efforts are being made to create and implement alternative genetic systems with pairing components orthogonal to natural base pairs. Another approach conserves Watson-Crick pairing but substitutes one or all of the four letters of the DNA alphabet with modified components. This study analyzes the properties of a DZA DDD structure and reveals interesting findings regarding stability, hydration, structure, and dynamics.
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: Scadoxus multiflorus is traditionally used for respiratory problems and this study investigated its alkaloidal composition. A previously undescribed alkaloid and fourteen known ones were identified. Some of the alkaloids exhibited weak antiviral activity against SARS-CoV-2, highlighting the potential of S. multiflorus as a source for anti-SARS-CoV-2 Amaryllidaceae alkaloid scaffolds.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Mengmeng Wang, Kunyu Qu, Peipei Zhao, Xin Yin, Yiwei Meng, Piet Herdewijn, Chao Liu, Lixin Zhang, Xuekui Xia
Summary: Gemcitabine prodrugs with modifications on the 4-N-amino group by employing an acetylated L- or D-lysine moiety masked by different substitutions were synthesized. These prodrugs showed higher anticancer activity than gemcitabine in A549 lung cells and exhibited potent activity against BxPC-3 pancreatic cells. They also showed lower toxicity towards normal cells and improved stability in various metabolic environments. Overall, acetylated lysine conjugated gemcitabine prodrugs could be promising leads for new anticancer drugs.
RSC MEDICINAL CHEMISTRY
(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
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: A new alkaloid, along with 17 known alkaloids, was isolated and identified from Pancratium maritimum using advanced probabilistic methods and spectroscopic techniques. Assessment of their anti-SARS-CoV-2 activity and cytotoxicity revealed several compounds with weak antiviral potency at non-toxic concentrations, while some compounds showed cytotoxicity.
PHYTOCHEMISTRY LETTERS
(2023)
