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Synthesis and anti(myco)bacterial activity of novel 5,5-diphenylpyrrolidine N-aroylthiourea derivatives and a functionalized hexahydro-1H-pyrrolo[1,2-c]imidazole

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Abstract

In this paper, five novel 5,5-diphenylpyrrolidine N-aroylthiourea derivatives were synthesized by stereoselective cycloaddition of N-diphenylmethylene-protected glycine methyl ester and methyl acrylate, and subsequent coupling with aroylisothiocyanates. The cis-stereochemistry of one of the heterocyclic thiourea derivatives was characterized by single crystal X-ray diffraction studies. The compounds showed antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Aeromonas hydrophila, Escherichia. coli and Acinetobacter baumannii with minimum inhibitory concentration values in the range of 62.5–1000 μg/mL against these bacterial strains. Antimycobacterial activity of the compounds was investigated against the M. tuberculosis H37Rv strain and all compounds exhibited antimycobacterial activity with a minimum inhibitory concentration value of 80 μg/mL. Additionally, methyl 5,5-diphenylhexahydro-1-oxo-3-thioxo-1H-pyrrolo[1,2-c]imidazole-6-carboxylate was synthesized by cyclization reaction of the 5,5-diphenylpyrrolidine N-aroylthiourea derivatives in the presence of hydrazine monohydrate and exhibited antibacterial activity with a minimum inhibitory concentration value of 62.5 μg/mL against the same bacterial strains and exhibited antimycobacterial activity with a minimum inhibitory concentration value of 80 μg/mL against the M. tuberculosis H37Rv strain.

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Acknowledgements

This work is a part of Duygu Erşen master thesis and we are thankful to Mersin University (project grant BAP-SBE TEB (DE) 2014-4 YL) and the Scientific and Technological Research Council of Turkey (TÜBİTAK, project grant 214Z289) for financial support.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Pharmacy, Mersin University, Mersin, Turkey

    Duygu Erşen, Müge Gemili & Yahya Nural

  2. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Mersin University, Mersin, Turkey

    Mahmut Ülger

  3. Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium

    Sven Mangelinckx

  4. Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey

    Ertan Şahin

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  1. Duygu Erşen
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  2. Mahmut Ülger
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Correspondence to Yahya Nural.

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Erşen, D., Ülger, M., Mangelinckx, S. et al. Synthesis and anti(myco)bacterial activity of novel 5,5-diphenylpyrrolidine N-aroylthiourea derivatives and a functionalized hexahydro-1H-pyrrolo[1,2-c]imidazole. Med Chem Res 26, 2152–2160 (2017). https://doi.org/10.1007/s00044-017-1907-9

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