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Development of a general and efficient route to highly lipophilic benzoxazole-2ylphosphonates and their antineoplastic properties

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Abstract

As a continuation of our efforts to discover and develop the 2-substituted-5,7-di-tert-butyl-2,3-dihydrobenzo[d]oxazol-2-ylphosphonate series of apoptosis inducers as potential anticancer agents, we explored new substitutions at the 2- and 3-positions of the oxazole ring to identify the development of antitumor candidates. This modification, in combination with synthesizing their relevant 2-benzoxazaphosphole 2-oxides and enaminophosphonates, resulted in obtaining an ensemble of 13 new phosphonates in high yields (70–76 %). The synthesized phosphonates were analyzed using the reversed-phase, high performance liquid chromatography method for the lipophilicity measurement (logK) as a prediction tool. Later on, selected compounds were evaluated as antitumor agents at a dose of 10 µmol cm−3 against breast, prostate, and melanoma carcinoma cell lines. The results were discussed in terms of structure–activity relationships.

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Acknowledgments

The authors gratefully acknowledge the financial support by the National Research Centre, Dokki, Cairo Egypt, project # 10010101. The authors also like to thank the Central Lab, School of Pharmacy, Alexandria University, Egypt, and the National Cancer Institute, NY, USA for carrying out the pharmacological screening.

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Authors and Affiliations

  1. Chemical Industries Division, National Research Centre, Dokki, Cairo, 12311, Egypt

    Reham F. Barghash, Neven A. Ganoub & Wafaa M. Abdou

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  1. Reham F. Barghash
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  2. Neven A. Ganoub
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  3. Wafaa M. Abdou
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Correspondence to Wafaa M. Abdou.

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Barghash, R.F., Ganoub, N.A. & Abdou, W.M. Development of a general and efficient route to highly lipophilic benzoxazole-2ylphosphonates and their antineoplastic properties. Monatsh Chem 145, 1621–1630 (2014). https://doi.org/10.1007/s00706-014-1233-6

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  • DOI: https://doi.org/10.1007/s00706-014-1233-6

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