Appl Biochem Biotechnol DOI 10.1007/s12010-014-1307-2

Synthesis, Antibacterial, Antiurease, and Antioxidant Activities of Some New 1,2,4-Triazole Schiff Base and Amine Derivatives Bahar Bilgin Sokmen & Nurhan Gumrukcuoglu & Serpil Ugras & Huseyin Sahin & Yasemin Sagkal & Halil Ibrahim Ugras

Received: 21 April 2014 / Accepted: 15 October 2014 # Springer Science+Business Media New York 2014

Abstract The acylhydrazone compound named ethyl N′-furan-2-carbonylbenzohydrazonate was synthesized by the condensation of ethyl benzimidate hydrochloride with furan-2carbohydrazide. The treatment of the acylhydrazone with hydrazine hydrate afforded 4amino-3-furan-2-yl-5-phenyl-1,2,4-triazole. The usage of this compound with various aromatic aldehydes resulted in the formation of 4-arylidenamino-3-furan-2-yl-5-phenyl-1,2,4triazoles. Sodium borohydride reduction of 4-arylidenamino derivatives afforded 4alkylamino-3-furan-2-yl-5-phenyl-1,2,4-triazoles. The obtained products were identified by FT-IR, 1H-NMR, 13C-NMR. A series of compounds were evaluated for their antibacterial, antiurease, and antioxidant activities. The results showed that the synthesized new compounds had effective antiurease and antioxidant activities. Keywords Acyl hydrazone . 1,2,4-triazole . Schiff base . Reduction . Urease inhibition activity . Antioxidant activity

Electronic supplementary material The online version of this article (doi:10.1007/s12010-014-1307-2) contains supplementary material, which is available to authorized users.

B. B. Sokmen (*) : Y. Sagkal Department of Chemistry, Faculty of Arts and Sciences, Giresun University, 28049 Giresun, Turkey e-mail: [email protected] N. Gumrukcuoglu Vocational School of Health Sciences, 61080 Trabzon, Turkey

S. Ugras Department of Field Crops, Faculty of Agriculture and Natural Science, Düzce University, 81620 Düzce, Turkey H. Sahin Espiye Vocational School, Giresun University, 28600 Giresun, Turkey H. I. Ugras Department of Chemistry, Faculty of Arts and Sciences, Düzce University, 81620 Düzce, Turkey

Appl Biochem Biotechnol

Introduction There is an increasing demand for the preparation of new antibacterial agents due to the developing resistance toward conventional antibiotics [1–3]. The synthesis of 1,2,4-triazole derivatives has attracted widespread attention due to their diverse biological activities, including antibacterial, anti-inflammatory, analgesic, and antitumoral [4–8]. Therefore, we have synthesized some 1,2,4-triazole derivatives possessing antibacterial activity [9, 10]. Small molecules are suitable as precursors for the preparation of novel compounds that can possess some biological properties. For instance, ethyl benzimidate hydrochloride 1 has been used intensively as starting material for the preparation of 1,2,4-triazole derivatives in our laboratories [11, 12]. It is known that the compound 1 can react easily with the compounds bearing an amino group to form 1,2,4-triazole or 1,3,4-thiadiazole derivatives. In addition to this, the treatment of iminoester hydrochlorides with hydrazide-type compounds produces hydrazones, which are useful intermediates for further ring closure [13, 14]. The metalloenzyme urease (urea amidohydrolase EC 3.5.1.5) is a nickel-containing enzyme that catalyzes the hydrolysis of urea to ammonia and carbon dioxide. Urease is widely distributed in nature and is found in a variety of plants, algae, fungi, and bacteria [15, 16]. The ammonia generated may severely disturb metabolic functions in a large number of animal tissues and organs [17, 18]. Ammonia is involved in the formation of infection stones in the urinary tract, which cause significant health problems and damage [19, 20]. Some studies indicate that urease inhibitors also have the potential to replace the current treatment for peptic ulcer [21], which is expensive and prone to development of antibiotic resistances. In the near past, a number of compounds have been proposed as urease inhibitors to reduce environmental problems and enhance the uptake of urea nitrogen by plants [22] and health problems. Free radical oxidative processes also play a significant pathological role in causing human disease. Many disease manifestations have been correlated with oxidative tissue damage. Antioxidants are widely studied for their capacity to protect organisms and cells from damage induced by oxidative stress during metabolism. In this present study, we have synthesized some new 1,2,4-triazole compounds and antiurease, and antioxidant activities for the newly synthesized compounds have been evaluated.

Materials and Methods General Melting points were determined on a Barnstead Electrothermal melting point apparatus and are uncorrected. 1H-NMR and 13C-NMR spectra (δ, ppm) were recorded on a Varian Mercury 200 MHz spectrophotometer using tetramethylsilane as the internal reference. The IR spectra (υ, cm−1) were obtained with a Perkin-Elmer 1600 FTIR spectrometer in KBr pellets. The necessary chemicals were purchased from Merck and Fluka. Ethyl benzimidate hydrochloride 1 was synthesized using a published method [9]. Antioxidant activities of samples were determined in a spectrophotometer (UV-1240, Shimadzu, Japan). Ethyl N′-Furan-2-Carbonylbenzohydrazonate (2) To the solution of ethyl benzimidate hydrochloride 1 (10 mmol) in absolute, ethanol was added the solution of furan-2-carbohydrazide (10 mmol) in absolute ethanol and the mixture was stirred at 0–5 °C for 6 h. Then, the precipitated ammonium chloride 35–40 °C under reduced pressure, a white solid was obtained.

Appl Biochem Biotechnol

This crude product was recrystallized from petroleum ether to afford compound 2 (yield 4.98 g, 66.22 %). M.p. 153–154 °C; IR (KBr) cm−1 3345 (ν NH), 1687 (ν C=O), 1604 (ν C=N), 758-708 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 1.34 (t, 3H, CH3), 4.09 (q, 2H, CH2), Ar–H [6.68 (d, 1H), 7.45–7.51 (m, 1H), 7.54– 7.60 (m, 4H), 7.66 (d, 1H), 7.91 (d, 1H)], 10.29 (s, 1H, NH); 13C-NMR (DMSO-d6) δ (ppm) 167.85 (C=O), 161.92 (C=N), Ar–C [138.14 (C), 135.46(C), 131.20 (CH), 129.48 (2CH), 129.32 (CH), 128.54 (CH), 128.41 (CH), 112.77 (CH) 112.36 (CH)], 63.74 (OCH2), 15.86 (CH3). 4-Amino-3-Furan-2-yl-5-Phenyl-1,2,4-Triazole (3) Compound 2 (0.005 mol) was added to a solution of hydrazine hydrate (0.01 mol) in 1-propanol (50 mL), and the mixture was refluxed for 24 h. After cooling, a precipitate formed was filtered off, dried, and washed with benzene (20 mL). The product was then recrystallized from 1-propanol to give compound 3 (yield 3.05 g, 78.00 %). M.p. 167–168 °C; IR (KBr) cm−1 3355–3288 (ν NH2), 1630, 1613 (ν 2C=N), 767–691 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 6.28 (s, 2H, NH2), Ar–H [6.72 (t, 1H), 7.29 (d, 1H), 7.49–7.54 (m, 3H), 7.92 (d, 1H), 7.96-8.04 (m, 2H)]; 13 C-NMR (DMSO-d6) δ (ppm) 154.22, 148.57 (2C, triazole C3, C5), Ar–C [145.06 (CH), 142.12 (C), 130.21 (CH), 129.09 (2CH) 128.97 (2CH), 127.65 (C), 112.34 (CH), 112.21 (CH)]. Synthesis of Schiff Bases (4a–c) The corresponding aldehyde (0.01 mol) was added to a solution of compound 3 (0.005 mol) in glacial acetic acid (20 mL), and the mixture was refluxed for 4 h. After cooling, the mixture was poured into a beaker containing ice water (100 mL). The precipitate formed was filtered. After drying in vacuo, the product was recrystallized from an appropriate solvent to give the desired compound. 3-Phenyl-5-(Furan-4-yl)-4-(4-Chlorobenzylidenamino)-4H-1,2,4-Triazole (4a) (Yield 1.28 g, 73.99 %). M.p. 155–156 °C; IR (KBr) cm−1 1598, 1560 (ν 2C=N), 809 (1,4 di substitue arom. ring), 776-697 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) Ar–H [6.67 (d,1H), 6.95 (d, 1H), 7.47–7.51 (m, 3H), 7.62–7.69 (m, 2H), 7.78–7.81 (m, 2H), 7.85 (t, 1H), 7.88– 7.96 (m, 2H)], 8.81 (s, 1H, N=CH); 13C-NMR (DMSO-d6) δ (ppm) 171.06 (N=CH), 150.39, 143.82 (2C, triazole C3, C5), Ar–C [141.31 (C), 139.10 (C), 131.53 (2CH), 130.84 (C), 130.72 (CH), 130.31 (2CH), 130.17 (2CH), 129.62 (2CH), 128.97 (CH), 128.26 (C), 113.25 (CH), 112.66 (CH)]. 3-Phenyl-5-(Furan-4-yl)-4-(2-Hydroxy-1-Naphthylidenamino)-4H-1,2,4-Triazole (4b) (Yield 1.30 g, 69.15 %). M.p. 151–152 °C; IR (KBr) cm−1 3320 (ν OH), 1624,1601 (ν 2C=N), 766–695 (mono substitue arom. ring), 748 (1,2 di substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) Ar–H [7.20 (d,1H), 7.35 (d, 2H), 7.50 (t, 1H), 7.60 (t, 1H), 7.86 (d, 2H), 7.90–8.05 (m, 3H), 8.10 (d, 2H), 8.90 (d, 2H)], 9.21 (s, 1H, N=CH), 9.76 (s, 1H, OH); 13C-NMR (DMSO-d6) δ (ppm) 168.12 (N=CH), 152.79, 150.28 (2C, triazole C3, C5), Ar–C [160.80 (C), 152.16 (CH), 143.80 (CH), 139.92 (C), 137.12 (CH), 131.51 (C), 129.88 (2CH), 129.10 (CH), 129.02 (CH), 128.91 (2CH), 128.15 (C), 124.76 (CH), 124.18 (CH), 123.77 (C), 118.22 (CH), 116.14 (CH), 108.09 (C), 107.15 (CH)]. 3-Phenyl-5-(Furan-4-yl)-4-(4-Methoxybenzylidenamino)-4H-1,2,4-Triazole (4c) (Yield 1.30 g, 76.47 %). M.p. 169–170 °C; IR (KBr) cm−1 1589, 1566 (ν 2C=N), 807 (1,4 di substitue arom. ring), 770-693 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 3.84 (s, 3H, OCH3), Ar–H [6.65 (d,1H), 6.90 (d, 1H), 7.10 (d, 2H), 7.46–7.50 (m, 3H), 7.64–

Appl Biochem Biotechnol

7.70 (m, 1H), 7.76–7.82 (m, 2H), 7.84–7.90 (m, 2H)], 8.70 (s, 1H, N=CH); 13C-NMR (DMSO-d6) δ (ppm) 168.62 (N=CH), 149.45, 148.64 (2C, triazole C3, C5), Ar–C [164.02 (C), 135.97 (CH), 135.12 (CH), 134.99 (C), 131.83 (2CH), 130.04 (2CH), 129.53 (2CH), 126.56 (C), 124.97 (C), 123.16 (CH), 122.04 (CH), 115.48 (2CH)], 56.33 (OCH3). Synthesis of Reduced Compounds (5a–c) The corresponding compounds (4a–c) (0.005 mol) were dissolved in dried methanol (50 mL), and NaBH4 (0.01 mol) was added in small portions to this solution. The mixture was refluxed for 20 min and then allowed to cool. After evaporation at 30–35 °C under reduced pressure, the solid residue was washed with cold water. After drying in vacuo, the solid product was recrystallized from an appropriate solvent to afford the desired compound. 3-Phenyl-5-(Furan-4-yl)-4-(4-Chlorobenzylamino)-4H-1,2,4-Triazole (5a) (Yield 0.40 g, 80.00 %). M.p. 145-146 °C; IR (KBr) cm−1 3291 (ν NH), 1599, 1558 (ν 2C=N), 811 (1,4 di substitue arom. ring), 763-692 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 3.92 (d, 2H, CH2), 6.74 (t, 1H, NH), Ar–H [6.95 (d, 2H), 7.17 (d, 2H), 7.25 (g, 2H), 7.48-7.55 (m, 3H), 7.87–7.89 (m, 2H), 7.96 (d, 1H)]; 13C-NMR (DMSO-d6) δ (ppm) 149.75, 148.49 (2C, triazole C3, C5), Ar–C [138.54 (C), 135.15 (C), 131.42 (C), 131.39 (2CH), 130.72 (2CH), 130.24 (CH), 130.10 (CH), 130.00 (2CH), 129.80 (2CH), 129.63 (2CH), 126.41 (C)], 54.13 (CH2). 3-Phenyl-5-(Furan-4-yl)-4-(2-Hydroxy-1-Naphthylamino)-4H-1,2,4-Triazole (5b) (Yield 0.43 g, 86.00 %). M.p. 174–175 °C; IR (KBr) cm−1 3318 (ν OH), 3264 (ν NH), 1626, 1598 (ν 2C=N), 778–695 (mono substitue arom. ring), 746 (1,2 di substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 4.37 (d, 2H, CH2), 6.85 (t, 1H, NH), Ar–H [7.03 (d, 2H), 7.24 (t, 2H), 7.31-7.36 (m, 3H), 7.62 (d, 2H), 7.69 (m, 2H), 7.82-7.84 (m, 3H)], 9.76 (s, 1H, OH); 13CNMR (DMSO-d6) δ (ppm) 153.53, 151.71 (2C, triazole C3, C5), Ar–C [156.87 (C), 134.47 (C), 134.16 (C), 132.14 (2CH), 130.23 (CH), 129.82 (2CH), 128.84 (CH), 128.72 (2CH), 128.56 (C), 126.92 (CH),126.80 (C), 123.21, (CH), 122.97 (CH), 118.26 (CH), 116.52 (2CH), 113.27 (C)], 45.17 (CH2). 3-Phenyl-5-(Furan-4-yl)-4-(4-Methoxybenzylamino)-4H-1,2,4-Triazole (5c) (Yield 0.38 g, 76.00 %). M.p. 187–188 °C; IR (KBr) cm−1 3290 (ν NH), 1611, 1560 (ν 2C=N), 800 (1,4 di substitue arom. ring), 762-695 (mono substitue arom. ring); 1H-NMR (DMSO-d6) δ (ppm) 3.67 (s, 3H, OCH3), 3.84 (d, 2H, CH2),7.06 (t, 1H, NH), Ar–H [6.70-6.75 (m, 3H), 6.90 (m, 2H), 7.25 (d, 1H), 7.51–7.55 (m, 3H), 7.92–7.96 (m, 3H)]; 13C-NMR (DMSO-d6) δ (ppm) 153.81, 147.52 (2C, triazole C3, C5), Ar–C [159.53 (C), 141.96 (C), 130.89 (2CH), 130.54 (CH), 129.18 (2CH), 128.69 (CH), 128.64 (2CH), 127.92 (C), 127.50 (C), 114.33 (2CH), 112.56 (CH), 112.34 (CH)], 55.73 (OCH3), 54.72 (CH2).

Microbial Strains and Antibacterial Activity The synthesized compounds were tested individually against 11 gram-positive and gramnegative bacteria species. The bacterial strains used in this study were obtained from the American Type Culture Collection (ATCC) and were as follows: Bacillus subtilis (B. subtilis) (ATCC 6633), Enterococcus faecalis (E. faecalis) (ATCC 29212), Staphylococcus aureus (S. aureus) (ATCC 25923), Staphylococcus epidermidis (S. epidermidis) (ATCC 12228), Escherichia coli (E. coli) (ATCC 25922), Klebsiella pneumonia (K. pneumonia) (ATCC 13883), Pseudomonas aeruginosa (P. aeruginosa) (ATCC 27853), Proteus vulgaris

Appl Biochem Biotechnol

(P. vulgaris) (ATCC 13315), Salmonella typhimurium (S. typhimurium) (ATCC 14028), Yersinia pseudotuberculosis (Y. pseudotuberculosis) (ATCC 911), and Enterobacter cloacae (E. cloaceae) (ATCC 13047). All synthesized compounds were weighed and dissolved in dimethyl sulfoxide (DMSO) to prepare stock solutions. Antibacterial activity was screened by agar well diffusion method [23, 24]. Furthermore, the antibiotic ampicillin (60 mg/mL) was used as positive control, and DMSO was used as negative control. The control groups were tested against the microorganisms. Each experiment was performed in triplicate. Urease Inhibitory Activity Urease inhibitory activity was determined according to Van Slyke and Archilbald [25].

Antioxidant Activity Ferric Reducing Antioxidant Power (FRAP) Assay The antioxidant activities of the samples were determined by FRAP assay [26]. The method is based on the measurement of the iron-reducing capacities of the compounds. Working FRAP reagent was prepared as required by mixing 25 mL of 0.3 M acetate buffer at pH 3.6 with 2.5 mL of 10 mM/L 2,4,6-tripyridyl-S-triazine (TPTZ) solution in 40 mM/L HCl and 2.5 mL of 20 mM/L FeCl3·6H2O. An amount of 100 μL of the sample was mixed with 3 mL of freshly prepared FRAP reagent. Then, the reaction mixture was incubated at 37 °C for 4 min. After that, the absorbance was determined at 593 nm against a blank that was prepared using distilled water and incubated for 1 h instead of 4 min. A calibration curve was used, using an aqueous solution of ferrous sulfate FeSO4·7H2O concentrations in the range of 100–1000 μM, r=0.9966. In order to make a comparison, FeSO4·7H2O was also tested under the same conditions as a standard antioxidant compound, FRAP values were expressed as μmol of FeSO4·7H2O equivalent of g sample. Scavenging of Free Radical (DPPH) Assay Radical scavenging activity of samples against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical was spectrophotometrically at 517 nm. First time, the method was used by Blois [27], developed and modified by Miller [28]. The assay is based on the color change of the DPPH solution from purple to yellow as the radical is deactivated by the antioxidants. Briefly, various concentrations (0.75 mL) of compound extracts were mixed with 0.75 mL of a 0.1-mM of DPPH in methanol. Radical scavenging activity was measured by using Trolox, BHT as standards, and the values are expressed as SC50, the concentration of the samples that causes 50 % scavenging of DPPH radical.

Results and Discussion In this study, the compound 2 was synthesized from the reaction of ethyl benzimidate hydrochloride 1, which was obtained by a published method [9], with furan-2-

Appl Biochem Biotechnol

carbohydrazide and its structure was established by FTIR, 1H-NMR, and 13C-NMR techniques (Scheme 1). The compound 3 was obtained by treatment of the compound 2 with hydrazine hydrate. The reaction was carried out in 1-propanol at refluxing temperature for 24 h, and the desired 4amino-3-furan-2-yl-5-phenyl-1,2,4-triazole 3 was yielded (Scheme 1). The compound 3 was converted to its Schiff bases (4a−c) by refluxing with 4-chlorobenzaldehyde, 2-hydroxy-1naphthaldehyde, and 4-methoxybenzaldehyde in acetic acid (Scheme 1). Previously, we obtained the Schiff bases of 1,2,4-triazole derivative. The synthesis of compounds (5a–c) was performed by the reduction of only the exocyclic azomethine bond of the Schiff bases (4a–c) (Scheme 1). These reduction reactions were conducted in considerably milder conditions. IR spectra showed the –NH2 bands of compound 3 in the 3126–3355 cm−1 region and the C=N bands of (4a–c) in the 1514–1624 cm−1 region. The 1H-NMR characteristic signals of 3 were observed at δ 6.01–6.28 (s, 2H, NH2). The 13C-NMR signals for the triazole C3, C5 were recorded at δ 148–154. 13C-NMR signals for the –N=CH group of compounds (4a–c) were recorded at δ 167–171. Arylmethylamino derivatives (5a–c) showed IR absorption bands

Scheme 1 Synthesized all ligands

Appl Biochem Biotechnol

around 3200–3300 cm−1 (υNH). The 1H-NMR characteristic signals of 5a–c were observed as a triplet at δ 6.74–7.07 (t, 1H, NH) and as a doublet at δ 3.58–4.37 (d, 2H, CH2). The NH– CH2– carbon signals of compounds (5a–c) were recorded between δ 45–56. Antibacterial activity was measured using the standard method of agar well diffusion, compound 2 has a moderate activity against E. faecalis, P. vulgaris, and B. subtilis but it has higher activity against E. coli and K. pneumonia. Furthermore, compounds 3 and 5c have a moderate activity against S. typhimurium and P. vulgaris too. Unfortunately, the other compounds have not any inhibition activity. Antibacterial activity results were given in Table 1. Almost all compounds showed moderate to good urease inhibitory activity (Table 2). The inhibition was increased with increasing triazole concentration. Lower IC50 values indicate higher enzyme inhibitor activity. Compound 4a proved to be the most potent showing an enzyme inhibition activity with an IC50 =0.0399±0.0049 μM. The least active compound 5b had an IC50 =0.0958±0.0025 μM. Triazoles have been regarded as structural type inhibitors of urease [22]. Our previous studies have shown that the triazole compounds yield highly potent inhibitors of urease [29, 30]. In this study, eight compounds were studied and also evaluated for antioxidant activity by two assays which were Ferric reducing antioxidant power (FRAP) and scavenging of free radical (DPPH). In four samples that were 2, 3, 4a, and 5c, antioxidant activity was determined. Result ranges of FRAP assay were 43.43– 869.65 μmol FeSO4·7H2O/g sample and about DPPH, 4376.08±26.551 μM. According to the results, 2 and 3 compounds had the highest activity among others. Due to radical effect, 50 % scavenging activity was determined in DPPH assay. The best value of SC50 was measured in compound 3. Because of the low SC50, the value of samples shows a high antioxidant effect (Table 3).

Table 1 Antimicrobial screening data for the synthesized compounds (2, 3, 4a–c, 5a–c) Bacteria

Zone of inhibition* 2

3

4a

4b

4c

5a

5b

5c

Amp –

Enterobacter cloacae

















Enterococcus faecalis

8 mm















26

Salmonella typhimurium



9 mm













19

Escherichia coli

15 mm















15

Staphylococcus epidermidis

















*

Proteus vulgaris

9 mm













9 mm

25

Yersinia pseudotuberculosis

















*

Staphylococcus aureus Pseudomonas aeruginosa

– –

– –

– –

– –

– –

– –

– –

– –

35 32

Klebsiella pneumonia

15 mm

















Bacillus subtilis

9 mm















31

DMSO has no values for negative control Amp ampicillin (60 mg/mL) *Not determined

Appl Biochem Biotechnol Table 2 The urease inhibitory activity of different concentrations of triazole derivatives (2, 3, 4a–b, 5a–b) Compounds

Triazole derivatives concentration (μg/mL)

Inhibition (%)*

IC50 (μM)*

2

0.00001 0.0001 0.001 0.01 0.00001 0.0001 0.001 0.01

36.65±0.870 38.61±0.764 40.94±0.276 43.77±0.354 34.69±2.093 40.99±0.347 45.14±0.325 46.97±1.117

0.0813±0.0006

0.00001 0.0001 0.001 0.01 0.00001 0.0001 0.001 0.01

32.88±0.856 37.60±0.771 40.98±1.633 45.87±1.365 31.21±1.499 35.65±0.651 40.19±1.527 44.02±1.358

4c

0.00001 0.0001 0.001 0.01

24.15±1.443 28.84±0.849 33.02±0.212 35.12±0.969

0.0873±0.0095

5a

0.00001 0.0001 0.001 0.01

22.83±0.438 30.72±1.527 33.51±0.453 35.91±1.047

0.078±0.0035

5b

0.00001 0.0001 0.001 0.01

24.12±1.358 27.63±0.863 30.65±0.530 33.14±1.032

0.0958±0.0025

5c

0.00001 0.0001 0.001 0.01

17.64±0.601 22.38±1.740 31.47±0.636 32.74±0.820

0.0763±0.010

3

4a

4b

0.0595±0.0071

0.0399±0.0049

0.0438±0.0050

*Mean±SD

Conclusions In our study, new 1,2,4-triazole derivatives have been synthesized, and their antibacterial, antiurease, and antioxidant activities were evaluated. The results showed that the synthesized new 1,2,4-triazole derivatives had antioxidant, antibacterial, and antiurease activities. For reason, new 1,2,4-triazole derivatives may be considered as a main urease inhibitory and free radical scavenger. Therefore, these compounds could be used as a source of antioxidant, antibacterial, and antiurease in pharmaceutical and agriculture industries. Correlation The results were presented as mean values and standard deviations (mean±SD). Data and regression analyses were performed with Microsoft Office Excel 2003 (Microsoft Corporation, Redmond, WA). A result of correlation, p value was calculated as −0.57. A negative result means when FRAP value increases, IC50 value decreases.

Appl Biochem Biotechnol Table 3 The antioxidant activities of triazole derivatives (2, 3, 4a–c, 5a–c) Compounds

FRAP (μmol FeSO4·7H2O/g sample)*

DPPH SC50 (μM)*

2

869.65±0.013

5381.97±30.975

3

684.42±0.010

4376.08±26.551

4a

305.84±0.010

8802.11±31.358

4b 4c

NA NA

NA NA

5a

NA

NA

5b

NA

NA

5c

43.43±0.010

13337.95±219.441

BHT



20.008±13.331

Troloks



11.033±11.214

*Mean±SD NA not active

Conflict of Interest The authors declare no financial or other relationship that might lead to a conflict of interest.

References 1. Klimesova, V., Zahajka, L., Waisser, K., Kaustova, J., & Mollmann, U. (2004). II Farmaco, 59, 279–288. 2. Zani, F., Vicini, P., & Incerti, M. (2004). European Journal of Medicinal Chemistry, 39, 135–140. 3. Tehranchian, S., Akbarzadeh, T., Fazeli, M. R., Jamalifar, H., & Shafiee, A. (2005). Bioorganic & Medicinal Chemistry Letters, 15, 1023–1025. 4. Awad, L. F., & El Ashry, S. H. (1998). Carbohydrate Researchs, 312, 9–22. 5. Amir, M., & Shikha, K. (2004). European Journal of Medicinal Chemistry, 39, 535–545. 6. Palaska, E., Sahin, G., Kelicen, P., Durlu, N. T., & Altınok, G. (2002). II Farmaco, 57, 101–107. 7. Holla, B. S., Poorjary, K. N., Rao, B. S., & Shivananda, M. K. (2002). European Journal of Medicinal Chemistry, 37, 511–517. 8. Henichart, J. P., Houssin, R., & Berier, J. L. (1986). Journal of Heterocyclic Chemistry, 23, 1531–1533. 9. Gumrukcuoglu, N., Serdar, M., Celik, E., Sevim, A., & Demirbas, N. (2007). Turkish Journal of Chemistry, 31(3), 335–348. 10. Serdar, M., Gumrukcuoglu, N., Karaoglu, S. A., & Demirbas, N. (2007). Turkish Journal of Chemistry, 31, 315–326. 11. Bekircan, O., & Gümrükçüoğlu, N. (2005). Indian Journal of Chemistry, 44B, 2107–2113. 12. Ocak, M., Gümrükçüoğlu, N., Ocak, Ü., Buschmann, H. J., & Schollmeyer, E. (2008). Journal of Solution Chemistry, 37, 1489–1497. 13. Weidinger, H., & Kranz, J. (1963). Chemische Berichte, 96(4), 1064–1070. 14. Gümrükçüoğlu, N., Uğraş, S., Uğraş, H. I., & Cakır, U. (2012). Journal of Inclusion Phenomena and Macrocyclic Chemistry, 73, 359–367. 15. Zerner, B. (1991). Bioorganic Chemistry, 19, 116–131. 16. Krajewska, B., Van-Eldik, R., & Brindell, M. (2012). Journal of Biological Inorganic Chemistry, 17, 1123– 1134. 17. Visek, W. J. (1984). Journal of Dairy Science, 67(3), 481–498. 18. Kleiner, D., Traglauer, A., & Domm, S. (1998). Bulletin de I’Institut Pasteur, 96(4), 257–265. 19. Mobley, L. T. H., Island, M. D., & Hausinger, R. P. (1995). Microbiological Review, 59, 451–480. 20. McLean, R. J. C., Nickel, J. C., Cheng, K. J., & Costerton, J. W. (1988). CRC Critical Review in Microbiology, 16(1), 37–79.

Appl Biochem Biotechnol 21. Vaira, D., Holton, J., Ricci, C., Baset, C., Gatta, L., Perna, F., Tampieri, M. A., & Miglioli, M. (2002). Alimentary Pharmacology & Therapeutics, 16, 105–113. 22. Amtul, Z., & Rasheed, M. (2004). Biochemical and Biophysical Research Communications, 319, 1053– 1063. 23. Chung, K. T., Thomasson, W. R., & Wu-Yuan, C. D. (1990). Journal of Applied Bacteriology, 69, 498–503. 24. Rabe, T., Mullholland, D., & van Staden, J. (2002). Journal of Ethnopharmacology, 80, 91–94. 25. Van Slyke, D. D., & Archibald, R. M. (1944). Journal of Biological Chemistry, 154, 623–642. 26. Benzie, I. F. F., & Strain, J. J. (1999). Methods in Enzymology, 299, 15–27. 27. Blois, M. S. (1958). Nature, 181, 1199–1200. 28. Miller, N. J., Rice-Evans, C. A., & Davies, M. J. (1993). Clinical Science, 84, 407–412. 29. Bilgin Sokmen, B., Gumrukcuoglu, N., Ugras, S., Ugras, H. I., & Yanardag, R. (2013). Journal of Enzyme Inhibition and Medicinal Chemistry, 28, 72–77. 30. Gumrukcuoglu, N., Bilgin Sokmen, B., Ugras, S., Ugras, H. I., & Yanardag, R. (2013). Journal of Enzyme Inhibition and Medicinal Chemistry, 28, 89–94.

Synthesis, antibacterial, antiurease, and antioxidant activities of some new 1,2,4-triazole schiff base and amine derivatives.

The acylhydrazone compound named ethyl N'-furan-2-carbonylbenzohydrazonate was synthesized by the condensation of ethyl benzimidate hydrochloride with...
274KB Sizes 0 Downloads 11 Views