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Synthesis, characterization, and biological evaluation of new quinazolin-4-one derivatives hybridized with pyridine or pyran moiety

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Abstract

A new series of 2-(furan-2-yl)-4-oxoquinazolin-3-phenyl derivatives hybridized with pyridine 3a–d, 4a–d or pyran moiety 5a–d were synthesized; their structures were confirmed by spectral and elemental analysis. Cytotoxicity was evaluated on three cancer cell lines (HEPG2, HCT116 and MCF7) using the sulphorodamine-B assay method and doxorubicin as a reference drug. Compound 5d showed a closely similar activity to doxorubicin on MCF7; their IC50 values are 4.6 and 4.4 nmol/mL, respectively. In addition, compounds 4b and 4c exhibited a closely similar activity to doxorubicin on HEPG2 cancer cells; their IC50 values expressed in nmol/mL are 6.6, 6.7, and 5.7, respectively. Moreover, compound 4b (IC50 = 1.2 nmol/mL) was four times more potent than doxorubicin (IC50 = 4.8 nmol/mL) on HCT116, and compound 5d (IC50 = 0.2 nmol/mL) revealed potency equal to 24 times the potency of doxorubicin on the same cancer cell line. The most active compounds were screened against EGFR TK, and results showed that compound 5d was the most potent inhibitor; its percentage of inhibition was 95.6. Furthermore, compound 5d was docked into the EGFR binding site to explore its possible interactions with EGFR TK.

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Acknowledgments

We are grateful to Dr. Ahmed B. M. Mehany and Dr. Serag E. I. Ali for performing pharmacological screening.

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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

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  1. Marwa F. Ahmed
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  2. Amany Belal
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Correspondence to Amany Belal.

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Ahmed, M.F., Belal, A. Synthesis, characterization, and biological evaluation of new quinazolin-4-one derivatives hybridized with pyridine or pyran moiety. Res Chem Intermed 42, 659–671 (2016). https://doi.org/10.1007/s11164-015-2048-8

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  • DOI: https://doi.org/10.1007/s11164-015-2048-8

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