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Design, synthesis, molecular modeling and anti-breast cancer activity of novel quinazolin-4-one derivatives linked to thiazolidinone, oxadiazole or pyrazole moieties

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Abstract

6,8-Dibromo-2-(4-chlorophenyl)-quinazolin-4-one linked directly to oxadiazole 5, pyrazole 6 or through amide linkage to thiazolidinone 2a–d and 3a–h were synthesized; their chemical structures were confirmed by spectral and elemental analyses. Their anti-breast cancer activity was evaluated against human breast cancer cell line (MCF-7) using resazurin reduction method and doxorubicin as a reference drug. Linking quinazolin-4-one scaffold to oxadiazole or pyrazole gave compounds 5 and 6 with a closely similar activity as doxorubicin; their IC50 was 23, 22 and 22 nmol/ml, respectively; however, the hybridization of quinazolin-4-one with thiazolidinone gave much better activity than doxorubicin. The most active compounds of the hybrid molecules between quinazolin-4-one and thiazolidinone are 2c,d and 3a,f. Their IC50 range was (3–9 nmol/ml). In an attempt to explore the mode of action of the best active compounds, docking on the ATP binding site of EGFR was performed. In vitro screening of these four compounds against EGFR tyrosine kinases showed inhibitory activity range 54–77.2 %.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt

    Marwa F. Ahmed

  2. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62514, Egypt

    Amany Belal

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Taif University, Taif, 21974, Kingdom of Saudi Arabia

    Amany Belal

  4. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo, Egypt

    Mahmoud Youns

Authors
  1. Marwa F. Ahmed
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  2. Amany Belal
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  3. Mahmoud Youns
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Correspondence to Marwa F. Ahmed or Amany Belal.

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Ahmed, M.F., Belal, A. & Youns, M. Design, synthesis, molecular modeling and anti-breast cancer activity of novel quinazolin-4-one derivatives linked to thiazolidinone, oxadiazole or pyrazole moieties. Med Chem Res 24, 2993–3007 (2015). https://doi.org/10.1007/s00044-015-1357-1

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  • DOI: https://doi.org/10.1007/s00044-015-1357-1

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