Synthesis and biological activity of hydrazide-hydrazones and their corresponding 3-Acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles

Koçyiğit-Kaymakçıoğlu B., Oruç-Emre E. E., Ünsalan S., Tabanca N., Khan S. I., Wedge D. E., ...More

Medicinal Chemistry Research, vol.21, no.11, pp.3499-3508, 2012 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 11
  • Publication Date: 2012
  • Doi Number: 10.1007/s00044-011-9882-z
  • Journal Name: Medicinal Chemistry Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3499-3508
  • Keywords: Hydrazide-hydrazones, 1,3,4-Oxadiazoles, Anti-inflammatory, Cytotoxicity, Antioxidant, Antifungal
  • Istanbul Medipol University Affiliated: No


Various 3-Acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles (11-20) were prepared by the reaction of aryl substituted hydrazones of 4-fluorobenzoic acid hydrazide (1-10) with acetic anhydride. The structures of the synthesized compounds 11-20, were confirmed by UV, IR, 1 H-NMR and mass spectroscopic methods. Antifungal evaluation of the hydrazide-hydrazones 1-10 and corresponding 3-Acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles 11-20, against clinical and standard Candida pathogens have been performed by using agar diffusion to indentify the active compounds, which were later subjected to a broth microdilution assay to justify the activity level in terms of minimum inhibitory concentrations (MIC). 4-Fluorobenzoic acid [(5-bromothiophen-2-yl)methylene]hydrazide, showed the highest inhibitory activity against Candida albicans (MIC: 125 μg/ml), and when compared with ketoconazole. In addition, bioauthographic antifungal activity against plant pathogenic fungi such as Colletotrichum, Botrytis, Fusarium, and Phomopsis was conducted. 4-Fluorobenzoic acid [(5-bromothiophen-2-yl)methylene]hydrazide was the most active analog against P. viticola with 91%inhibition at 30 lM after 144 h. Furthermore, known and the newly synthesized compounds were also screened through a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. 3-Acetyl-5-(4-fluorophenyl)-2-(3- hydroxy-4-methoxyphenyl)-2,3-dihydro-1,3, 4-oxadiazole, showed a strong inhibition of NF-jB-dependent transcription in SW1353 cells with IC50 value of 0.75 μg/ml. 4-Fluorobenzoic acid [(3-hydroxy-4-methoxyphenyl) methylene]hydrazide, and 3-Acetyl-5-(4-fluorophenyl)-2-(3-hydroxy-4- methoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole on intracellular ROS generation in PMA induced HL-60 cells demonstrated potent activity with IC50 values of 0.9 μg/ml. A strong inhibition of the activity of iNOS activity in LPS induced RAW 264.7 cells was observed for 3-Acetyl-5-(4-fluorophenyl)-2-(4-hydroxyphenyl) -2,3-dihydro-1,3,4-oxadiazole with IC 50 value of 0.3 μg/ml. © Springer Science+Business Media, LLC 2011.