Acta Pharm. 69 (2019) 277-285

 

full paper

Short communication

 

Antimicrobial assesment of aroylhydrazone derivatives in vitro

SAŠA POLOVIĆ, VANJA LJOLJIĆ BILIĆ, ANA BUDIMIR, DARKO KONTREC, NIVES GALIĆ and IVAN KOSALEC

ngalic@chem.pmf.hr; ikosalec@pharma.hr

1Agency for Medicinal Products and Medical Devices of Croatia, Zagreb, Croatia

2 Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb

Zagreb, Croatia

3 Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

4 Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, PO Box 180, HR-10002 Zagreb, Croatia

5 Department of Chemistry, Faculty of Science, University of Zagreb, Zagreb, Croatia

Accepted December 14, 2018

Published online February 11, 2019

 

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 ×10–2 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 (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.

 

Keywords: aroylhydrazones, antimicrobial, antibiofilm, MDR strains