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<p>Adult T-cell leukemia/lymphoma (ATLL) has low overall survival, underscoring the need for the development of novel approaches. Present study aimed to investigate anti-proliferative effects of entinostat and its newly synthesized analogs on ATLL cells. Computational analyses were conducted to identify the potential molecular targets of entinostat, and construct a protein–protein interaction network. Then, enrichment analyses were performed, and the expression of CDK4 was assessed in MT-2 cells. Molecular docking and dynamics simulations were carried out to predict the interactions of entinostat and its novel analogs with target proteins. For <i>in vitro</i> studies, at first quinoline-based benzamide derivatives were synthesized. Then, MT-2 and normal cells were treated and their proliferation was evaluated by alamarBlue assay. Finally, flow cytometry was performed, and the expression of candidate genes was assessed by real-time PCR. Exploring potential targets of entinostat and pathogenic targets of ATLL revealed 51 overlapping molecules including CDK4. Volcano plot revealed over expression of CDK4 in MT-2 cells. Favorable and stable binding of entinostat and its analogs with the activation loop of CDK4 and the CDK-binding site of cyclin D1 was confirmed. Experimental studies revealed anti-proliferative effects of entinostat and analogs on MT-2 cells, confirmed by flow cytometry analysis and alterations in the expression of <i>BAX</i>, <i>CCND1</i>, and <i>BCL-2</i>. Present findings pave the way for the development of new drugs against ATLL, and provide evidence that justifies further preclinical evaluations of entinostat and its novel analogs.</p>

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Entinostat and novel analogs: preclinical evidence for anti-proliferative activity in adult T-cell leukemia/lymphoma

  • 期刊论文

  • 发表日期：

    2025年6月17日

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  • Sajad Goudarzi,
  • Zahra Nasiri Sarvi,
  • Hossein Ayatollahi,
  • Razieh Ghodsi,
  • Zeinab Noroozi,
  • Mohammad Reza Keramati,
  • Fatemeh B. Rassouli

摘要

Adult T-cell leukemia/lymphoma (ATLL) has low overall survival, underscoring the need for the development of novel approaches. Present study aimed to investigate anti-proliferative effects of entinostat and its newly synthesized analogs on ATLL cells. Computational analyses were conducted to identify the potential molecular targets of entinostat, and construct a protein–protein interaction network. Then, enrichment analyses were performed, and the expression of CDK4 was assessed in MT-2 cells. Molecular docking and dynamics simulations were carried out to predict the interactions of entinostat and its novel analogs with target proteins. For in vitro studies, at first quinoline-based benzamide derivatives were synthesized. Then, MT-2 and normal cells were treated and their proliferation was evaluated by alamarBlue assay. Finally, flow cytometry was performed, and the expression of candidate genes was assessed by real-time PCR. Exploring potential targets of entinostat and pathogenic targets of ATLL revealed 51 overlapping molecules including CDK4. Volcano plot revealed over expression of CDK4 in MT-2 cells. Favorable and stable binding of entinostat and its analogs with the activation loop of CDK4 and the CDK-binding site of cyclin D1 was confirmed. Experimental studies revealed anti-proliferative effects of entinostat and analogs on MT-2 cells, confirmed by flow cytometry analysis and alterations in the expression of BAX, CCND1, and BCL-2. Present findings pave the way for the development of new drugs against ATLL, and provide evidence that justifies further preclinical evaluations of entinostat and its novel analogs.