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A convenient synthesis, reactions and biological evaluation of novel pyrazolo[3,4-b]selenolo[3,2-e]pyrazine heterocycles as potential anticancer and antimicrobial agents

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Abstract

A novel series of 5-amino-6-substituted-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazines (3a–e) was synthesized by the reaction of the chloro pyrazolo[3,4-b]pyrazine carbonitrile 1 with selenium element in the presence of sodium borohydride and ethanol, followed by the reaction with α-halo alkylating agents to produce the selanyl-alkylated derivatives 2a–e. The latter compounds underwent Thorpe-Ziegler cyclization upon heating with ethanolic sodium ethoxide solution to afford the target selenolopyrazolopyrazine compounds. The 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazine-6-carboxamide (3b) was used as a versatile precursor for synthesis of new heterocyclic fused to the pyrazoloselenolopyrazine moiety namely: pyrimidine and imidazopyrimidine. Assignment of the chemical structures for the newly synthesized compounds was confirmed on the bases of elemental and spectral techniques including FT-IR, 1H NMR, 13C NMR, and mass spectra. Furthermore, certain compounds were screened for their antimicrobial activity which revealed remarkable activities against various pathogenic strains of bacteria and fungi. Alternatively, some of these compounds exhibited promising anticancer action against some colon and breast cancer cells.

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Acknowledgements

The authors are very grateful to Prof. Dr./Etaify A. Bakhite, Chairman of Chemistry Department for the facilities provided to us, Also, thanks was extended to all the staff members of Chemistry Department for their sincere effort during this work.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt

    Remon M. Zaki, Mokhtar A. Abdul-Malik, Shaban M. Radwan & Adel M. Kamal El-Dean

  2. Chemistry Department, Faculty of Science, Taiz University, Taiz, Yemen

    Mokhtar A. Abdul-Malik

  3. Zoology Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt

    Saber H. Saber

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  1. Remon M. Zaki
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Correspondence to Remon M. Zaki.

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Zaki, R.M., Abdul-Malik, M.A., Saber, S.H. et al. A convenient synthesis, reactions and biological evaluation of novel pyrazolo[3,4-b]selenolo[3,2-e]pyrazine heterocycles as potential anticancer and antimicrobial agents. Med Chem Res 29, 2130–2145 (2020). https://doi.org/10.1007/s00044-020-02635-z

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