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Synthesis, antimicrobial evaluation, and molecular docking studies of new tetrahydrocarbazole derivatives

Research on Chemical Intermediates volume 42, pages 1363–1386 (2016)Cite this article

Abstract

New derivatives bearing 6,7,8,9-tetrahydro-5H-carbazole moiety functionalized with different side chains and/or heterocycles were synthesized and evaluated for their in vitro antibacterial and antifungal activities. The reaction of the starting acid hydrazide 3 with benzoyl chloride yielded the corresponding compound 4. A series of Schiff’s bases 5a–d were synthesized by the treatment of 3 with different aromatic or heterocyclic aldehydes. Furthermore, acid hydrazide 3 was refluxed with various acid anhydrides to give the derivatives 6a–c. Esterification of 3 with ethyl chloroformate produced the corresponding ester analogue 7 which was further reacted with hydrazine hydrate to give the carbonohydrazide derivative 8. Also, new derivatives carrying tetrahydrocarbazol-benzohydrazide core in conjugation with various heterocyclic ring systems: 5-aminopyrazole, thiadiazole oxadiazole, 1,3,4-triazol-2-thione, and triazolo[3,4-b]thiadiazole 9, 10, 13, 14, 15, 16, and 17, respectively, were synthesized. Antimicrobial evaluation exhibited that most of the synthesized compounds produced promising antibacterial and moderate to weak antifungal activities when compared with ciprofloxacin and ketoconazole as standard antibacterial and antifungal drugs. Dual efficient potency was gained by compounds 6a, 6c, and 12. A molecular docking study of some of the compounds was carried out inside the active site of DNA gyrase protein.

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Authors and Affiliations

  1. Therapeutical Chemistry Department, National Research Center, Dokki, Cairo, 12622, Egypt

    Neama A. Mohamed, Walaa S. El-Serwy & Somaia S. Abd El-Karim

  2. Chemistry of Natural and Microbial Products Department, National Research Center, Dokki, Cairo, 12622, Egypt

    Ghada E. A. Awad

  3. Green Chemistry Department, National Research Centre, Cairo, 12622, Egypt

    Samia A. Elseginy

  4. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, UK

    Samia A. Elseginy

Authors
  1. Neama A. Mohamed
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Mohamed, N.A., El-Serwy, W.S., Abd El-Karim, S.S. et al. Synthesis, antimicrobial evaluation, and molecular docking studies of new tetrahydrocarbazole derivatives. Res Chem Intermed 42, 1363–1386 (2016). https://doi.org/10.1007/s11164-015-2090-6

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  • DOI: https://doi.org/10.1007/s11164-015-2090-6

Keywords

  • Tetrahydrocarbazole
  • Carbohydrazide
  • Antimicrobial activity
  • Molecular docking