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Synthesis of 1-benzhydryl piperazine derivatives and evaluation of their ACE inhibition and antimicrobial activities

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Abstract

This study presents the synthesis of 14 new 1,4-disubstituted piperazine derivatives from allyl bromides of Baylis–Hillman adduct and 4,4-disubstituted benzhydryl piperazines. All the synthesized compounds were further screened for in vitro ACE inhibitor and antimicrobial activities. Among the synthesized piperazine derivatives, compound 12h showed moderate ACE inhibitor activity as compared to the standard, angiotensin-converting enzyme inhibitor (Sigma). The kinetic data (K m, K i and V max values) of enzyme inhibition for compound 12h and ACE inhibitor standard were also determined. Similarly, all compounds were screened against different bacterial strains. Compounds 12a, 12b, 12d, 12h and 12i showed excellent to moderate activity against various tested bacterial strains. Compounds 12b and 12i showed broad spectrum of antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, S. aureus MLS 16, Escherichia coli, Bacillus subtilis and Klebsiella planticola, while compounds 12a, 12d and 12i showed promising activity against P. aeruginosa (MIC value of 8.96 μM), S. aureus (MIC value of 42.2 μM) and S. aureus MLS 16 (MIC value of 81.3 μM), respectively. The remaining compounds showed activity at a concentration of >491 μM.

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Acknowledgements

The authors thank the Director, CSIR, Indian Institute of Chemical Technology, for the facilities and encouragement. AS, SNK, PS and PSS acknowledge the CSIR, New Delhi, for research fellowships.

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Authors and Affiliations

  1. Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    Amlipur Santhoshi, Singam Naveen Kumar, Partha Sarathi Sadhu & Vaidya Jayathirtha Rao

  2. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India

    Pombala Sujitha, Yedla Poornachandra & C. Ganesh Kumar

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  1. Amlipur Santhoshi
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  2. Singam Naveen Kumar
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  3. Pombala Sujitha
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  5. Partha Sarathi Sadhu
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Correspondence to C. Ganesh Kumar or Vaidya Jayathirtha Rao.

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Santhoshi, A., Kumar, S.N., Sujitha, P. et al. Synthesis of 1-benzhydryl piperazine derivatives and evaluation of their ACE inhibition and antimicrobial activities. Med Chem Res 23, 3207–3219 (2014). https://doi.org/10.1007/s00044-013-0895-7

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  • DOI: https://doi.org/10.1007/s00044-013-0895-7

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