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Synthesis, characterization, and antimicrobial evaluation of a small library of ferrocene-containing acetoacetates and phenyl analogs: the discovery of a potent anticandidal agent

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Abstract

A library of 16 2-substituted methyl acetoacetates containing ferrocenyl or phenyl units was designed to disclose differences in the antimicrobial activity of ferrocene-containing compounds and their phenyl analogs. Two methyl acetoacetates, whose structures do not contain an aromatic nucleus, were also included in order to probe the inherent activity of the scaffold itself. The acetoacetates were synthesized (low-to-good yields) and fully characterized by spectral (MS, IR, UV–Vis, 1D and 2D NMR) and electrochemical (cyclic voltammetry) techniques. Single-crystal X-ray analysis has been performed for methyl 2-acetyl-2-(ferrocenylmethyl)-5-methylhex-4-enoate. All compounds have demonstrated in vitro antimicrobial activity against six bacterial (three Gram-positive and three Gram-negative) and two fungal strains with minimal inhibitory concentration values of 0.0050–20.6 \(\upmu \hbox {mol mL}^{-1}\). The most active compound was 2-acetyl-2-(ferrocenylmethyl)-4-methylpent-4-enoate whose activity was comparable to that of nystatin against the yeast Candida albicans. Agglomerative hierarchical clustering statistical analysis of the antimicrobial assay data demonstrated that ferrocene-containing compounds have statistically different and greater antimicrobial activity when compared to their phenyl analogs.

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Acknowledgments

This work was funded by the Ministry of Education, Science and Technological Development of Serbia (Project 172061). This publication is a part of Marko Z. Mladenović’s PhD thesis under the supervision of Niko Radulović.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 , Nis, Serbia

    Niko S. Radulović & Marko Z. Mladenović

  2. Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 , Nis, Serbia

    Zorica Stojanović-Radić

  3. Laboratory of Theoretical Physics and Condensed Matter Physics, Vinča Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 , Belgrade, Serbia

    Goran A. Bogdanović

  4. Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 , Kragujevac, Serbia

    Dragana Stevanović & Rastko D. Vukićević

Authors
  1. Niko S. Radulović
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  2. Marko Z. Mladenović
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  3. Zorica Stojanović-Radić
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  4. Goran A. Bogdanović
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  5. Dragana Stevanović
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  6. Rastko D. Vukićević
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Correspondence to Niko S. Radulović.

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Radulović, N.S., Mladenović, M.Z., Stojanović-Radić, Z. et al. Synthesis, characterization, and antimicrobial evaluation of a small library of ferrocene-containing acetoacetates and phenyl analogs: the discovery of a potent anticandidal agent. Mol Divers 18, 497–510 (2014). https://doi.org/10.1007/s11030-014-9511-0

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  • DOI: https://doi.org/10.1007/s11030-014-9511-0

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