Abstract
In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Parabacteroides distasonis and Fusubacterium nucleatum pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases. Some derivatives were even more active than the antimicrobial drugs secnidazole and metronidazole. Therefore, the compounds under study are suitable for in vivo evaluation and the microorganisms should be classified as susceptible to them. Electrochemical studies on the reduction of the nitro group revealed that the compounds show comparable reduction potentials, which are in the same range of the bio-reducible drugs secnidazole and benznidazole. The nitro group reduction potential is more favorable for the copper(II) complexes than for the starting ligands. Hence, the antimicrobial activities of the compounds under study might in part be related to intracellular bio-reduction activation. Considering the increasing resistance rates of anaerobic bacteria against a wide range of antimicrobial drugs, the present work constitutes an important contribution to the development of new antibacterial drug candidates.
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Acknowledgements
The authors gratefully acknowledge CNPq, CAPES-PNPD, FAPEMIG and INCT-INOFAR (Proc. CNPq 573.364/2008-6) for financial support and student grants. Funding was provided by CNPq (Grant Numbers 421902/2016-7 and 303746/2013-0).
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Supplementary material 1 (DOCX 1644 kb) Supplementary Information (SI) reports X-ray crystallography data of HL6, as well as the FT-IR, NMR and HRMS spectra of 2 and HL3–HL8 and FT-IR spectra of complexes (Ca–Cf). SI also contains the cyclic voltammograms of 2, HL3–HL8 and Ca–Cf. CCDC reference number 1575237 contains the supplementary crystallographic data for HL6. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
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Oliveira, A.A., Oliveira, A.P.A., Franco, L.L. et al. 5-Nitroimidazole-derived Schiff bases and their copper(II) complexes exhibit potent antimicrobial activity against pathogenic anaerobic bacteria. Biometals 31, 571–584 (2018). https://doi.org/10.1007/s10534-018-0106-6
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DOI: https://doi.org/10.1007/s10534-018-0106-6