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Medicinal Chemistry Research

, Volume 24, Issue 7, pp 2993–3007 | Cite as

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

  • Marwa F. Ahmed
  • Amany Belal
  • Mahmoud Youns
Original Research

Abstract

6,8-Dibromo-2-(4-chlorophenyl)-quinazolin-4-one linked directly to oxadiazole 5, pyrazole 6 or through amide linkage to thiazolidinone 2ad and 3ah 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 %.

Keywords

Quinazolin-4-one Thiazolidinone Oxadiazole Pyrazole MCF-7 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyHelwan UniversityCairoEgypt
  2. 2.Department of Medicinal Chemistry, Faculty of PharmacyBeni-Suef UniversityBeni SuefEgypt
  3. 3.Department of Pharmaceutical Chemistry, Faculty of PharmacyTaif UniversityTaifKingdom of Saudi Arabia
  4. 4.Department of Biochemistry and Molecular Biology, Faculty of PharmacyHelwan UniversityCairoEgypt

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