2. Academic Validation
  3. Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma

Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma

  • Eur J Med Chem. 2018 Jul 15:155:516-530. doi: 10.1016/j.ejmech.2018.05.042.
Mai I Shahin 1,  Joyeeta Roy 2,  Maha Hanafi 3,  Dongyao Wang 4,  Urarika Luesakul 5,  Yifeng Chai 6,  Nongnuj Muangsin 7,  Deena S Lasheen 8,  Dalal A Abou El Ella 9,  Khaled A Abouzid 8,  Nouri Neamati 10
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
  • 2 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States.
  • 3 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
  • 4 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States; School of Pharmacy, Second Military Medical University, 200433, Shanghai, China.
  • 5 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States; Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 6 School of Pharmacy, Second Military Medical University, 200433, Shanghai, China.
  • 7 Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 8 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
  • 9 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, 62511, Beni Suef, Egypt.
  • 10 Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, United States. Electronic address: neamati@umich.edu.
PMID: 29908444 DOI: 10.1016/j.ejmech.2018.05.042
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.

Keywords

Autophagy; Chloroquine; Esophageal squamous cell cancer; Quinoline-4-carboxamide; Structure-activity Relationships.

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