دورية أكاديمية
Discovery of a new 1-(phenylsulfonyl)-1H-indole derivative targeting the EphA2 receptor with antiproliferative activity on U251 glioblastoma cell line.
| العنوان: | Discovery of a new 1-(phenylsulfonyl)-1H-indole derivative targeting the EphA2 receptor with antiproliferative activity on U251 glioblastoma cell line. |
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| المؤلفون: | Guidetti L; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Castelli R; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Zappia A; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Ferrari FR; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Giorgio C; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Barocelli E; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Pagliaro L; Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy; Ematologia e CTMO, Azienda Ospedaliero Universitaria di Parma, Parma, Italy; Translational Hematology and Chemogenomics (THEC), Università di Parma, Parma, Italy., Vento F; Translational Hematology and Chemogenomics (THEC), Università di Parma, Parma, Italy; Dipartimento di Scienze Mediche, Università di Ferrara, Ferrara, Italy., Roti G; Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy; Ematologia e CTMO, Azienda Ospedaliero Universitaria di Parma, Parma, Italy; Translational Hematology and Chemogenomics (THEC), Università di Parma, Parma, Italy., Scalvini L; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Vacondio F; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Rivara S; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy., Mor M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy; Microbiome Research Hub, Università di Parma, Parma, Italy., Lodola A; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy. Electronic address: alessio.lodola@unipr.it., Tognolini M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy. Electronic address: massimiliano.tognolini@unipr.it. |
| المصدر: | European journal of medicinal chemistry [Eur J Med Chem] 2024 Oct 05; Vol. 276, pp. 116681. Date of Electronic Publication: 2024 Jul 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| مواضيع طبية MeSH: | Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemical synthesis , Antineoplastic Agents*/chemistry , Cell Proliferation*/drug effects , Drug Discovery* , Drug Screening Assays, Antitumor* , Glioblastoma*/drug therapy , Glioblastoma*/pathology , Glioblastoma*/metabolism , Indoles*/pharmacology , Indoles*/chemistry , Indoles*/chemical synthesis , Receptor, EphA2*/antagonists & inhibitors , Receptor, EphA2*/metabolism, Humans ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Molecular Docking Simulation ; Molecular Structure ; Structure-Activity Relationship ; Hydrocarbons, Fluorinated/chemical synthesis ; Hydrocarbons, Fluorinated/chemistry ; Hydrocarbons, Fluorinated/pharmacology |
| مستخلص: | In our continuing effort devoted at developing agents targeting the EphA2 receptor by means of protein-protein interaction (PPI) inhibitors, we report here the design and synthesis of a new class of l-β-homotryptophan conjugates of 3-β-hydroxy-Δ 5 -cholenic acid bearing a set of arylsulfonyl substituents at the indole nitrogen atom. An extensive structure-activity relationship (SAR) analysis indicates that the presence of a bulky lipophilic moiety at the indole nitrogen is fundamental for improving potency on the EphA2 receptor, while abrogating activity on the EphB1-EphB3 receptor subtypes. A rational exploration, guided by the combined application of an experimental design on σ Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Massimiliano Tognolini reports financial support was provided by Italian Association for Cancer Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Docking; EphA2; Glioblastoma; Protein-protein interaction; SAR |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (EPHA2 protein, human) 0 (Indoles) EC 2.7.10.1 (Receptor, EphA2) 0 (Hydrocarbons, Fluorinated) |
| تواريخ الأحداث: | Date Created: 20240718 Date Completed: 20240809 Latest Revision: 20240814 |
| رمز التحديث: | 20240814 |
| DOI: | 10.1016/j.ejmech.2024.116681 |
| PMID: | 39024966 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2024.116681 |