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United States Department of Agriculture

Agricultural Research Service

Research Project: Chemistry of Natural Products for Nutraceutical Use, Pest Management and Crop Development

Location: Natural Products Utilization Research

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

Authors
item Kocyigit-Kaymakciogl, U -
item Oruc-Emre, Emime Elcin -
item Unsalan, Seda -
item Iscan, Gokalp -
item Demirci, Fatih -
item Rollas, Sevim -
item Tabanca, Nurhayat -
item Wedge, David
item Khan, Shabana -

Submitted to: Bioorganic and Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 4, 2011
Publication Date: November 20, 2011
Citation: Kocyigit-Kaymakciogl, U., Oruc-Emre, E., Unsalan, S., Iscan, G., Demirci, F., Rollas, S., Tabanca, N., Wedge, D.E., Khan, S.I. 2011. Synthesis and biological activity of hydrazide hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles. Bioorganic and Medicinal Chemistry. 1-10.

Interpretive Summary: In recent years, the five membered 1,3,4-oxadiazole heterocycles have gained importance due to their application in pharmaceutical chemistry. Therefore several 1,3,4-oxadiazole derivatives exhibited broad spectrum of biological activities such as antimicrobial, antituberculosis, analgesic, antiinflammatory, anticancer activities. Owing to their diverse biological properties, their synthesis has increased noticeably in recent years, we evaluated known hydrazide-hydrazone and newly synthesized 1,3,4-oxadiazole derivatives in a panel of bioassays that include, anti-inflammatory, antioxidant, cytotoxic and antifungal activities against human and plant pathogenic fungi. Several compounds showed good activity against human pathogens and anti-inflammatory activity. One compound , 4-fluorobenzoic acid [(5-bromothiophen-2-yl)methylene]hydrazide, demonstrated 91% inhibition at the highest concentration against Phomopsis viticola.

Technical Abstract: Various new 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 newly synthesized compounds 11-20, were confirmed by UV, IR and 1H NMR spectroscopic methods. Antifungal evaluation of the hydrazide-hydrazones 1-10 and corresponding new 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. Compound 9, 4-fluorobenzoic acid [(5-bromothiophen-2-yl)methylene]hydrazide, showed the highest inhibitory activity against Candida albicans (MIC: 0.125 mg/mL) when compared with positive control ketoconazole it showed the same inhibition potency. In addition, antifungal activity against plant pathogenic fungi such as Colletotrichum, Botrytis, Fusarium, and Phomopsis assays was also conducted. Compound 9 was the most active analog against P. viticola with 91% inhibition at 30 µM 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.Compound 16, 1-[5-(4-fluorophenyl)-2-(3-hydroxy-4-methoxyphenyl)-1,3,4-oxadiazol-3(2H)-yl]ethanone, showed a strong inhibition of NF-'B-dependent transcription in SW1353 cells with IC50 value of 0.75 µg/mL. Compounds 6, 4-fluorobenzoic acid [(4-hydroxy-3-methoxyphenyl)methylene]hydrazide, and 16 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 compound 14, 1-[5-(4-fluorophenyl)-2-(4-hydroxyphenyl)-1,3,4-oxadiazol-3(2H)-yl]ethanone, with IC50 value of 0.3 µg/mL.

Last Modified: 4/16/2014
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