Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma
Shahin, Mai I; Roy, Joyeeta; Hanafi, Maha; Wang, Dongyao; Luesakul, Urarika; Chai, Yifeng; Muangsin, Nongnuj; Lasheen, Deena S.; Neamati, Nouri; Khaled A M Abouzid; Abou El Ella, Dalal;
Abstract
No new and effective treatments have been approved for the treatment of esophageal squamous cell carcinoma (ESCC) in the past decade. Cisplatin and 5-fluoruracil are the most commonly used drugs for this disease. In order to develop a new class of drugs effective in our ESCC phenotypic screens, we began a systematic approach to generate novel compounds based on the 2-oxo-1,2-dihydroquinoline-4-carboxamide fragment. Herein, we report on the synthesis and initial assessment of 55 new analogues in two ESCC cell lines. Some of the active analogues with IC50 values around 10 μM were tested in three additional cell lines. Our structure-activity relationships revealed remarkable alterations in the anti proliferative activities upon modest chemical modifications and autophagy modulation is a suggested mechanism of action.
Other data
Title | Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma | Authors | Shahin, Mai I; Roy, Joyeeta; Hanafi, Maha; Wang, Dongyao; Luesakul, Urarika; Chai, Yifeng; Muangsin, Nongnuj; Lasheen, Deena S. ; Neamati, Nouri; Khaled A M Abouzid ; Abou El Ella, Dalal | Keywords | Structure-activity Relationships;Autophagy;Chloroquine;Esophageal squamous cell cancer;Quinoline-4-carboxamide | Issue Date | 15-Jul-2018 | Publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Journal | European Journal of Medicinal Chemistry | Volume | 155 | Start page | 516 | End page | 530 | ISSN | 0223-5234 | DOI | 10.1016/j.ejmech.2018.05.042 | PubMed ID | 29908444 | Scopus ID | 2-s2.0-85048317453 | Web of science ID | WOS:000441856300040 |
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