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Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives: assessment of their antimicrobial, antituberculosis and antioxidant activity

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Abstract

A new series of pyrazolo[1,2-b]phthalazine derivatives (4a–p) bearing the 5-aryloxypyrazole nucleus was synthesized by one-pot, three-component, base-catalyzed cyclo condensation reaction of 3-methyl-5-aryloxy-1-aryl-1H-pyrazole-4-carbaldehyde (1a–d), malononitrile or ethyl cyanoacetate (2a–b) and 2,3-dihydro-1,4-phthalazinedione (3a–b) in ethanol containing an eco friendly base, NaOH, in good to excellent yields. All synthesized compounds (4a–p) were duly characterized by physico-chemical parameters, 1H NMR, 13C NMR, FT-IR and LCMS techniques. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 4e, 4g, 4h, 4k and 4o exhibited excellent antimicrobial activity compared with first line drugs. In vitro antituberculosis activity was evaluated against Mycobacterium tuberculosis H37Rv, and compounds 4g and 4o emerged as the promising antimicrobial members with better antituberculosis activity. A brine shrimp bioassay was carried out to study the in vitro cytotoxic properties of the synthesized compounds. In vitro antioxidant activity was evaluated by the ferric-reducing antioxidant power method. Compounds 4c, 4d, 4g and 4h showed the highest antioxidant potencies.

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Acknowledgments

This work was financed by the National Natural Science Foundation of China (No. J1103512).

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Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People’s Republic of China

    Chetan B. Sangani, Jigar A. Makwana, Yong-Tao Duan, Nilesh J. Thumar, Meng-Yue Zhao & Hai-Liang Zhu

  2. Chemistry Department, Government Science College, Gandhinagar, 382015, Gujarat, India

    Yogesh S. Patel

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  1. Chetan B. Sangani
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  2. Jigar A. Makwana
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  3. Yong-Tao Duan
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  4. Nilesh J. Thumar
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  5. Meng-Yue Zhao
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  6. Yogesh S. Patel
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  7. Hai-Liang Zhu
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Correspondence to Chetan B. Sangani or Hai-Liang Zhu.

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Sangani, C.B., Makwana, J.A., Duan, YT. et al. Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives: assessment of their antimicrobial, antituberculosis and antioxidant activity. Res Chem Intermed 42, 2101–2117 (2016). https://doi.org/10.1007/s11164-015-2138-7

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  • DOI: https://doi.org/10.1007/s11164-015-2138-7

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