Antimicrobial assesment of aroylhydrazone derivatives in vitro

Open access

Abstract

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 IC 90 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 ×10−2 vs. 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 (IC 50 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.

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 A 95 (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;

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information


IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 177 177 97
PDF Downloads 75 75 28