Aroylhydrazones 1–13 were screened for antimicrobial and antibiofilm activities in vitro. N′-(2-hydroxy-phenylmethylidene)-3-pyridinecarbohydrazide (2), N′-(5-chloro-2-hydroxyphenyl-methylidene)-3-pyridinecarbohydrazide (10), N′-(3,5-chloro-2-hydroxyphenylmethylidene)-3-pyridinecarbohydrazide (11), and N′-(2-hydroxy-5-nitrophenylmethylidene)-3-pyridinecarbohydrazide (12) showed antibacterial activity against Escherichia coli, with MIC values (in µmol mL−1) of 0.18–0.23, 0.11–0.20, 0.16–0.17 and 0.35–0.37, resp. Compounds 11 and 12, as well as N′-(2-hydroxy-3-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (6) and N′-(2-hydroxy-5- methoxyphenylmethylidene)-3-pyridinecarbohydrazide (8) showed antibacterial activity against Staphylococcus aureus, with the lowest MIC values of 0.005–0.2, 0.05–0.12, 0.06–0.48 and 0.17–0.99 µmol mL−1. N′-(2-hydroxy-5-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (7) showed antifungal activity against both fluconazole resistant and susceptible C. albicans strains with IC90 range of 0.18–0.1 µmol mL−1. Only compound 11 showed activity against C. albicans ATCC 10231 comparable to the activity of nystatin (the lowest MIC 4.0 ×10−2vs. 1.7 × 10−2 µmol mL−1). Good activity regarding multi-resistant clinical strains was observed for compound 12 against MRSA strain (MIC 0.02 µmol mL−1) and compounds 2, 6 and 12 against ESBL+ E. coli MFBF 12794, with the lowest MIC for compound 12 (IC50 0.16 µmol mL−1). Anti-biofilm activity was found for compounds 2 (MBFIC 0.015–0.02 µmol mL−1 against MRSA) and 12 (MBFIC 0.013 µmol mL−1 against EBSL+ E. coli). In the case of compound 2 against MRSA biofilm formation, MBFIC values were comparable to those of gentamicin sulphate, whereas in the case of compound 12 and EBSL+ E. coli even more favourable activity compared to gentamicin was observed.
If the inline PDF is not rendering correctly, you can download the PDF file here.
1. Ł. Popiołek Hydrazide-hydrazones as potential antimicrobial agents: overview of the literature since 2010 Med. Chem. Res. 26 (2017) 287–301; DOI 10.1007/s00044-016-1756-y
2. M. K. Dahlgren C. E. Zetterström Å. Gylfe A. Linusson and M. Elofsson Statistical molecular design of a focused salicylidene acylhydrazide library and multivariate QSAR of inhibition of type III secretion in the Gram-negative bacterium Yersinia Bioorg. Med. Chem. 18 (2010) 2686–2703; https://doi.org/10.1016/j.bmc.2010.02.022
3. P. V. Bernhardt P. Chin P. C. Sharpe and D. R. Richardson Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity Dalton Trans. 30 (2007) 3232–3244; https://doi.org/10.1039/b704102k
4. K. Hruskova P. Kovarikova P. Bendova P. Haskova E. Mackova J. Stariat A. Vavrova K. Vavrova and T. Simunek Synthesis and initial in vitro evaluations of novel antioxidant aroylhydrazone iron chelators with increased stability against plasma hydrolysis Chem. Res. Toxicol. 24 (2011) 290–302; https://doi.org/10.1021/tx100359t
5. P. Kovaríkova Z. Mrkvičkova and J. Klimeš Investigation of the stability of aromatic hydrazones in plasma and related biological material J. Pharm. Biomed. Anal. 47 (2008) 360–370; https://doi.org/10.1016/j.jpba.2008.01.011
6. N. Galić A. Dijanošić D. Kontrec and S. Miljanić Structural investigation of aroylhydrazones in dimethylsulphoxide/water mixtures Spectrochim. Acta A95 (2012) 347–353; https://doi.org/10.1016/j.saa.2012.03.086
7. C. F. Da Costa A. C. Pinheiro M. V. De Almeida M. C. Lourenço and M. V. De Souza Synthesis and antitubercular activity of novel amino acid derivatives Chem. Biol. Drug Des. 79 (2012) 216–222; https://doi.org/10.1111/j.1747-0285.2011.01269.x
8. M. C. Mandewale B. Thorat Y. Nivid R. Jadhav A. Nagarsekar and R. Yamgar Synthesis structural studies and antituberculosis evaluation of new hydrazone derivatives of quinoline and their Zn(II) complexes J. Saudi Chem. Soc. 22 (2018) 218–228; https://doi.org/10.1016/j.jscs.2016.04.003
9. Y. Ozkay Y. Tunali H. Karaca and I. Işikdağ Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety Eur. J. Med. Chem. 45 (2010) 3293–3298; https://doi.org/10.1016/j.ejmech.2010.04.012
10. T. Benković A. Kenđel J. Parlov-Vuković D. Kontrec V. Chiş S. Miljanić and N. Galić Multiple dynamics of aroylhydrazone induced by mutual effect of solvent and light - spectroscopic and computational study J. Mol. Liq. 255 (2018) 18–25; https://doi.org/10.1016/j.saa.2017.09.038
11. T. Benković D. Kontrec V. Tomišić A. Budimir and N. Galić Acid-base properties and kinetics of hydrolysis of aroylhydrazones derived from nicotinic acid hydrazide J. Solution Chem. 45 (2016) 1227–1245; https://doi.org/10.1007/s10953-016-0504-8
12. European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) EUCAST Discussion Document E. Dis 5.1 Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution Clin. Microbiol. Infect. 9 (2003) 1–7; https://doi.org/10.1046/j.1469-0691.2003.00790.x
13. M. C. Arendrup J. Meletiadis J. W. Mouton K. Lagrou Petr Hamal J. Guinea and the Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing EUCAST Definitive Document E. Def. 7.3.1. January 2017 - Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Yeasts; http://www.eucast.org/ast_of_fungi/methodsinantifungalsusceptibilitytesting/susceptibility_testing_of_yeasts/; last access date December 13 2018.
14. J. Vlainić I. Kosalec K. Pavić D. Hadjipavlou-Litina E. Pontiki and B. Zorc Insights into biological activity of ureidoamides with primaquine and amino acid moieties J. Enzyme Inhib. Med. Chem. 33 (2018) 376–382; https://doi.org/10.1080/14756366.2017.1423067
15. S. Purser P. R. Moore S. Swallow and V. Gouverneur Fluorine in medicinal chemistry Chem. Soc. Rev. 37 (2008) 320–330;