Design, synthesis, chemical characterization, biological evaluation, and docking study of new 1,3,4-oxadiazole homonucleoside analogs
| Autor: | Mohamed Zahouily, Graciela Andrei, Hassan Ait Benhassou, Abdeladim Moumen, Mohamed Maatallah, Hassan B. Lazrek, Robert Snoeck, Az-Eddine El Mansouri, Ahmad Mehdi |
|---|---|
| Přispěvatelé: | Plante - microbe - environnement : biochimie, biologie cellulaire et écologie (PMEBBCE), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Moroccan Foundation for Advanced Science, Innovation and Research (MASCIR), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Herpesvirus 3
Human Receptor ErbB-2 Oxadiazole Antineoplastic Agents HL-60 Cells Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Biochemistry Antiviral Agents chemistry.chemical_compound Cell Line Tumor Genetics Humans 1 3 4-Oxadiazole Protein Kinase Inhibitors ComputingMilieux_MISCELLANEOUS Biological evaluation Cell Proliferation Oxadiazoles Molecular Structure 010405 organic chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Nucleosides General Medicine molecular docking [CHIM.MATE]Chemical Sciences/Material chemistry Combinatorial chemistry homonucleosides 3. Good health 0104 chemical sciences ErbB Receptors Molecular Docking Simulation anticancer activity Design synthesis chemistry Docking (molecular) Drug Design antiviral activity MCF-7 Cells Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Nucleosides, Nucleotides and Nucleic Acids Nucleosides, Nucleotides and Nucleic Acids, Taylor & Francis, 2020, 39 (8), pp.1088-1107. ⟨10.1080/15257770.2020.1761982⟩ Nucleosides, Nucleotides and Nucleic Acids, Taylor & Francis, 2020, pp.1-20. ⟨10.1080/15257770.2020.1761982⟩ |
| ISSN: | 1088-1107 1525-7770 1532-2335 |
| DOI: | 10.1080/15257770.2020.1761982⟩ |
| Popis: | Herein, we report the synthetic strategies and characterization of some novel 1,3,4-oxadiazole homonucleoside analogs that are relevant to potential antitumor and cytotoxic activities. The structure of all compounds is confirmed using various spectroscopic methods such as 1H-NMR, 13C-NMR, HRMS, and FTIR. These compounds were evaluated against three human cancer cell lines (MCF-7, SKBR3, and HL60 Cell Line). Preliminary investigations showed that the cytotoxic activity was markedly dependent on the nucleobase. Introduction of 5-Iodouracil 4g and theobromine 6b proved to be extremely beneficial even they were more potent than the reference drug (DOX). Also, the synthesized compounds were tested for their antiviral activities against the human varicella-zoster virus (VZV). The product 4h was (6-azauracil derivative) more potent to the reference (acyclovir) against the deficient TK - VZV strain by about 2-fold. Finally, molecular docking suggested that the anticancer activities of compounds 6b and 4g mediated by inhibiting dual proteins EGFR/HER2 with low micromolar inhibition constant Ki range. The 1,3,4-oxadiazole homonucleosides showed a strong affinity to binding sites of target proteins by forming H-bond, carbon-hydrogen bond, Pi-anion, Pi-sulfur, Pi-sigma, alkyl, and Pi-alkyl interactions. ispartof: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS vol:39 issue:8 pages:1088-1107 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|