Article
Microbiology
Yoshihiro Ojima, Naoki Yokota, Yuki Tanibata, Shinsuke Nerome, Masayuki Azuma
Summary: This study investigated the mechanism of toxicity of Toyocamycin (TM) and its analogs to Candida albicans. It was found that the absence of purine nucleoside transport activity from Saccharomyces cerevisiae (S. cerevisiae) made it less susceptible to TM and its analogs. However, when the concentrative nucleoside transporter (CNT) of Candida albicans (C. albicans) was expressed in S. cerevisiae, the sensitivity to TM and its analogs was restored. In addition, introducing human CNT3 into S. cerevisiae also made it sensitive to TM and its analogs. These findings enhance our understanding of the mechanisms of action of adenosine analogs toward Candida pathogens and human cells.
MICROBIOLOGY SPECTRUM
(2022)
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
Gustavo Daniel Campagnaro
Summary: After a period of decline in the interest for purine transporters in protozoa, the potential of tubercidin derivatives has sparked a new wave of interest in the subject recently. Extensive in vitro testing is being conducted on newly designed compounds against various pathogens, indicating a resurgence in using purine transporters for drug delivery in combating neglected diseases.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Applied
Dinesh J. Paymode, N. Vasudevan, Saeed Ahmad, Appasaheb L. Kadam, Flavio S. P. Cardoso, Justina M. Burns, Daniel W. Cook, Rodger W. Stringham, David R. Snead
Summary: This study presents a two-step synthesis of molnupiravir with high overall yield of 60%, emphasizing practical reaction and purification conditions. By limiting the total concentration of solvent and using environmentally friendly solvents, excellent throughput and sustainability were achieved in the operations.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Clara Boces-Pascual, Aida Mata-Ventosa, Mireia Martin-Satue, Loreto Boix, Meritxell Gironella, Marcal Pastor-Anglada, Sandra Perez-Torras
Summary: Downregulation of hCNT1 protein was found in both colorectal and pancreatic ductal adenocarcinoma, potentially regulated by miR-106a and miR-17, leading to chemoresistance to fluoropyrimidine-based treatments.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Chemistry, Medicinal
Leandro S. de Mariz e Miranda
Summary: This viewpoint proposes that molecules inhibiting nucleotide biosynthesis may sensitize virus-infected cells to antiviral nucleosides, potentially leading to the development of new combination therapies.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Linjie Yan, Ruiyuan Cao, Hongjie Zhang, Yuexiang Li, Wei Li, Xiaoyuan Li, Shiyong Fan, Song Li, Wu Zhong
Summary: Phosphoamidate derivatives of nucleoside NITD008 were synthesized and evaluated for their antiviral activities against EV71 and EV-D68, with compounds 15f and 151 showing the most promising results. Compound 151 demonstrated the highest selectivity index against both viruses, indicating its potential as a candidate for antiviral drug development in treating EV71 and EV-D68 infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Franck Amblard, Julia C. LeCher, Ramyani De, Shu Ling Goh, Chengwei Li, Mahesh Kasthuri, Nicolas Biteau, Longhu Zhou, Zahira Tber, Jessica Downs-Bowen, Keivan Zandi, Raymond F. Schinazi
Summary: This study reports the synthesis and evaluation of a series of novel NHC analogs for the treatment of early SARS-CoV-2 infections, among which Molnupiravir is approved for emergency use.
Article
Infectious Diseases
Henry Pertinez, Rajith K. R. Rajoli, Saye H. Khoo, Andrew Owen
Summary: This study utilized a mathematical model to simulate the intracellular pharmacokinetics of the active metabolite of favipiravir, revealing that despite rapid clearance of the parent drug from plasma, sufficient intracellular active metabolite may be maintained across the dosing interval. The predicted regimen of 1200 mg twice daily of favipiravir is estimated to maintain intracellular active metabolite concentrations above the Km for the SARS-CoV-2 polymerase for 9 days. Further evaluation of favipiravir in combination with other antivirals for SARS-CoV-2 treatment is recommended.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Julian Peter Mueller, Dirk Gruendemann
Summary: In this study, it has been demonstrated that the ergothioneine transporter ETT does not transport nucleosides but efficiently transports gemcitabine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marzuq A. Ungogo, Mustafa M. Aldfer, Manal J. Natto, Hainan Zhuang, Robyn Chisholm, Katy Walsh, MarieClaire McGee, Kayhan Ilbeigi, Jamal Ibrahim Asseri, Richard J. S. Burchmore, Guy Caljon, Serge Van Calenbergh, Harry P. De Koning
Summary: African Animal Trypanosomiasis (AAT) is a fatal livestock disease in Sub-Saharan Africa caused by Trypanosoma brucei brucei, T. vivax, and T. congolense. Limited treatment options and resistance threaten the control of this disease. In this study, the adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10) were characterized and their functional expression was demonstrated. The findings suggest that nucleoside chemotherapy for AAT is viable based on the similarities in nucleoside sensitivity among different parasite species and the interactions with nucleoside transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Kevin J. Sparrow, Rinu Shrestha, James M. Wood, Keith Clinch, Brett L. Hurst, Hong Wang, Brian B. Gowen, Justin G. Julander, E. Bart Tarbet, Alice M. McSweeney, Vernon K. Ward, Gary B. Evans, Lawrence. D. Harris
Summary: We report the antiviral activities of two iminovirs (antiviral imino-C-nucleosides) 1 and 2, structurally related to galidesivir (Immucillin A, BCX4430), for the first time. An iminovir containing the 4-aminopyrrolo[2,1-f ][1,2,4-triazine] nucleobase found in remdesivir showed submicromolar inhibition against multiple strains of influenza A and B viruses, as well as members of the Bunyavirales order. The ProTide prodrugs of iminovir monophosphates displayed poorer viral inhibition than their parent nucleosides in vitro. A synthesized iminovir 2 containing 4-aminopyrrolo[2,1-f][1,2,4-triazine] was used for preliminary in vivo studies, but it showed significant toxicity in BALB/ c mice and limited protection against influenza, indicating the need for further modification to improve its therapeutic value.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Microbiology
Jiaxin Qin, Zhanglei Cao, Xia Cai, Yu Fang, Baoju An, Xuelian Li, Yizhuo Zhang, Hongwei Tian, Wenzhuo Hu, Bing Yan, Jun Cai
Summary: Nucleoside transport is crucial for maintaining the balance of nucleosides and nucleobases within a cell. In this study, a novel transcription factor, NupR, was identified as the first GntR family transcription factor primarily involved in regulating nucleoside transport. NupR responds to diverse intracellular signals and controls nucleoside transport, playing a vital role in utilizing extracellular nucleosides and maintaining intracellular nucleoside homeostasis. Furthermore, NupR may also be involved in other pathways such as pH homeostasis, molybdenum cofactor biosynthesis, nitrate metabolism, and transport. Understanding the transport mechanism of nucleosides could have implications for the production of nucleosides, including antiviral drugs.
MICROBIOLOGY SPECTRUM
(2022)
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)
Review
Biochemistry & Molecular Biology
Mengbi Yang, Xin Xu
Summary: Nucleoside analogs are important antiviral agents, but their hydrophilicity and limited membrane permeability require the involvement of transporters in their pharmacokinetics. This review discusses the roles of transporters in the pharmacokinetics of 25 approved AVNAs and highlights the impact of co-administered inhibitors and genetic polymorphisms of transporters on AVNA pharmacokinetics. More research is needed to understand the roles of transporters in the distribution of AVNAs, especially in immune privileged compartments. Pharmacokinetic models can be useful in elucidating the complex factors affecting AVNA pharmacokinetics in clinical settings.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Balazs Vasko, Viktoria Juhasz, Beata Toth, Anita Kurunczi, Zsolt Fekete, Joseph Krisjanis Zolnerciks, Emese Kis, Remi Magnan, Axel Bidon-Chanal Badia, Marcal Pastor-Anglada, Eszter Hazai, Zsolt Bikadi, Ferenc Fulop, Peter Krajcsi
Review
Pharmacology & Pharmacy
Marcal Pastor-Anglada, Sandra Perez-Torras
FRONTIERS IN PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Sandra Perez-Torras, Aida Mata-Ventosa, Britt Drogemoller, Maja Tarailo-Graovac, Judith Meijer, Rutger Meinsma, Arno G. van Cruchten, Wim Kulik, Albert Viel-Oliva, Axel Bidon-Chanal, Colin J. Ross, Wyeth W. Wassermann, Clara D. M. van Karnebeek, Marcal Pastor-Anglada, Andre B. P. van Kuilenburg
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2019)
Article
Biochemistry & Molecular Biology
Natalia Grane-Boladeras, Declan Williams, Zlatina Tarmakova, Katarina Stevanovic, Linda A. Villani, Pedram Mehrabi, K. W. Michael Siu, Marcal Pastor-Anglada, Imogen R. Coe
Article
Multidisciplinary Sciences
Monica Pascual-Garcia, Ester Bonfill-Teixidor, Ester Planas-Rigol, Carlota Rubio-Perez, Raffaella Ludaro, Alexandra Arias, Isabel Cuartas, Ada Sala-Hojman, Laura Escudero, Francisco Martinez-Ricarte, Isabel Huber-Ruano, Paolo Nuciforo, Leire Pedrosa, Carolina Marques, Irene Brana, Elena Garralda, Maria Vieito, Massimo Squatrito, Estela Pineda, Francesc Graus, Carmen EspejoH, Juan Sahuquillo, Josep Tabernero, Joan Seoane
NATURE COMMUNICATIONS
(2019)
Article
Pharmacology & Pharmacy
Catalina M. Perello-Reus, Albert Catala, Liska Caviedes-Cardenas, Nerea Vega-Garcia, Mireia Camos, Sandra Perez-Torras, Marcal Pastor-Anglada
PHARMACOLOGICAL RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Adrian Christopher Jaramillo, Isabelle Hubeek, Richard Broekhuizen, Marcal Pastor-Anglada, Gertjan J. L. Kaspers, Gerrit Jansen, Jacqueline Cloos, Godefridus J. Peters
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
(2020)
Article
Biochemistry & Molecular Biology
Elena Guillen-Gomez, Irene Silva, Nuria Serra, Francisco Caballero, Jesus Leal, Alberto Breda, Rody San Martin, Marcal Pastor-Anglada, Jose A. Ballarin, Lluis Guirado, Montserrat M. Diaz-Encarnacion
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Oncology
E. Benaiges, V. Ceperuelo-Mallafre, A. Madeira, R. Bosch, C. Nunez-Roa, M. Ejarque, E. Maymo-Masip, I. Huber-Ruano, M. Lejeune, J. Vendrell, S. Fernandez-Veledo
Summary: Recent studies suggest that adipose-derived stem cells (ASCs) may serve as a link between obesity and cancer. Survivin, highly secreted by ASCs from obese subjects, drives a pro-tumoral phenotype in macrophages, leading to enhanced malignant characteristics of cancer cells. Survivin may serve as a molecular link between obesity and cancer and a novel marker for tumor-associated macrophages, with potential implications in cancer development.
Article
Biochemistry & Molecular Biology
Clara Boces-Pascual, Aida Mata-Ventosa, Mireia Martin-Satue, Loreto Boix, Meritxell Gironella, Marcal Pastor-Anglada, Sandra Perez-Torras
Summary: Downregulation of hCNT1 protein was found in both colorectal and pancreatic ductal adenocarcinoma, potentially regulated by miR-106a and miR-17, leading to chemoresistance to fluoropyrimidine-based treatments.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Margarida Terron-Puig, Isabel Huber-Ruano, Joan Sabadell-Basallote, Miriam Ejarque, Catalina Nunez-Roa, Elsa Maymo-Masip, Rosa Jorba, Carolina Serena, Joan Vendrell, Sonia Fernandez-Veledo
Summary: Dysfunctional adipocyte precursors play a crucial role in obesity- and aging-related inflammation. This study investigates the metabolic and inflammatory changes in human adipose-derived mesenchymal stromal cells (hASCs) from elderly and obese individuals. The findings suggest that both obesity and aging impair the differentiation potential of hASCs, and aging is associated with upregulation of glycolysis-related genes and increased secretion of pro-inflammatory molecules. Additionally, decreased expression of SIRT1 and SIRT6 proteins may contribute to the inflammatory state in hASCs from elderly subjects. Overall, a glycogen-SIRT1/6 signaling axis is identified as a driver of age-related inflammation in adipocyte precursors.
Review
Biochemistry & Molecular Biology
Marcal Pastor-Anglada, Aida Mata-Ventosa, Sandra Perez-Torras
Summary: The regulation of nucleotide pools is crucial for cellular functions. Mutations in genes encoding nucleoside and nucleobase transporters have been identified in certain rare diseases, causing various clinical manifestations. Understanding the physiological and molecular features of these transporter proteins helps in understanding the biochemical and clinical effects of these deficiencies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Isabel Huber-Ruano, Enrique Calvo, Jordi Mayneris-Perxachs, M-Mar Rodriguez-Pena, Victoria Ceperuelo-Mallafre, Lidia Cedo, Catalina Nunez-Roa, Joan Miro-Blanch, Maria Arnoriaga-Rodriguez, Aurelie Balvay, Claire Maudet, Pablo Garcia-Roves, Oscar Yanes, Sylvie Rabot, Ghjuvan Micaelu Grimaud, Annachiara De Prisco, Angela Amoruso, Jose Manuel Fernandez-Real, Joan Vendrell, Sonia Fernandez-Veledo
Summary: The study reveals that gut microbiota is a significant source of elevated succinate in obese individuals. Therapeutic treatments with selected bacteria can reduce circulating succinate levels in obese mice, and Odoribacter laneus shows promise as a probiotic to deplete succinate and improve glucose tolerance.
Review
Pharmacology & Pharmacy
Merce Brunet, Marcal Pastor-Anglada
Summary: The influence of pharmacogenetics in tacrolimus pharmacokinetics and pharmacodynamics needs further investigation to assist in predicting optimal dosage, personalized adjustment of the dose, and identifying high-risk patients. New strategies have been developed to improve personalized tacrolimus treatment, with lower doses associated with higher incidence of adverse events. Inconsistent genotype-phenotype relationships have been identified in tacrolimus pharmacodynamics.
Article
Physiology
Marcal Pastor-Anglada, Nerea Urtasun, Sandra Perez-Torras
COMPREHENSIVE PHYSIOLOGY
(2018)