Abstract
A series of glycosyl-substituted 1,3,4-oxadiazoles were synthesized by cyclization of glycosyl-acylthiosemicarbazides via a base-catalyzed reaction. The starting glycosyl-acylthiosemicarbazide derivatives were obtained by the reaction of glycosyl isothiocyanate with various hydrazides. The acetylcholinesterase (AChE) inhibitory activities of the products were tested by Ellman’s method. The most active compounds were subsequently evaluated for the 50% inhibitory concentration (IC50) values. N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole-2-amine (6i) possesses the best AChE -inhibition activity with an IC50 of 1.61±0.34 μm.
Introduction
Carbohydrates have long interested chemists and biochemists as a large natural resource [1], [2], [3], [4]. As an energy source and an element of many metabolic processes, sugars are present in every part of the human body [5]. D-glucosamine is a naturally occurring amino sugar [6], [7], one of the most abundant monosaccharides, and has been widely used in the prevention and/or treatment of rheumatoid arthritis and osteoarthritis [8], [9]. Furthermore, D-glucosamine exhibits a broad variety of bioactivities such as anti-inflammatory [10], anti-cancer [11] and anti-bacterial [12] properties and it suppresses tumor growth [13]. Modified carbohydrates provide access to potential mimetics of naturally occurring amino sugars and represent targets for the development of anti-oxidant [14], anti-acetylcholinesterase (AChE) [15], anti-proliferative [16] and other active agents [17], [18], [19], [20].
The emergence of heterocyclic compounds with novel structures may promote discovery of new drugs and treatment of stubborn diseases [21], [22], [23], [24]. Recently, the oxadiazole chemistry has been developed extensively. 1,3,4-Oxadiazoles structurally resemble amides and esters [25], and some compounds show similar pharmacokinetic properties [26], [27], [28], [29], [30], [31]. Moreover, recent studies have shown that a number of compounds containing the 1,3,4-oxadiazole skeleton act as monoamine oxidase inhibitors for the treatment of Alzheimer’s disease (AD) [32], [33], [34]. AD is a chronic, neurodegenerative disorder that causes an irreversible dementia in elderly people [35].
Researchers have been interested in molecular hybrid-based approaches to find new compounds of potential biological activities [36], [37]. Based on the aforementioned information, herein we report the design and synthesis of novel D-glucosamine/1,3,4-oxadiazole hybrids with the oxadiazole ring offering an important pharmacophore to discover new potent AChE inhibitors. The synthesized derivatives were evaluated by Ellman’s method for AChE inhibitors and to explore the influence of D-glucosamine against AChE inhibition.
Results and discussion
Chemistry
In the development of C2-glycosyl oxadiazoles, glycosyl isothiocyanate 3 was the critical intermediate compound. Our strategy began with an attempted synthesis of this starting material without protection of hydroxyl groups at D-glucosamine hydrochloride but, to our disappointment, this attempt failed. The benzyl group was used to protect the hydroxyl groups. 1,3,4,6-Tetra-O-benzyl-β-D-glucosamine hydrochloride 1 was synthesized according to the literature [38], [39]. Treatment of compounds 1 with triethylamine in acetonitrile was followed by the addition of carbon disulfide, which furnished dithiocarbamic acid salt 2. Subsequent reaction of 2 with tosyl chloride (p-TsCl) yielded the key glycosyl isothiocyanate immediate 3 (Scheme 1). Compound 3 was treated with various hydrazides 4 to yield the glycosyl acylthiosemicarbazide derivatives 5a–j. Cyclization of the intermediate products 5 in a base-catalyzed reaction afforded the glycosyl oxadiazole derivatives 6a–j in high yields (Scheme 2).
Biological activity
The AChE-inhibition activities of the compounds were evaluated in vitro by Ellman’s method [40] using the AChE extract from electric eel. The results are summarized in Table 1. Selected compounds were subsequently evaluated for the maximal inhibitory concentration, IC50, with tacrine and galantamine as the reference compounds. The results indicate that all compounds show higher inhibitory activities against AChE than the precursor compound n. The best compound 6i shows the highest activity with an IC50 value of 1.61±0.34 against AChE and inhibits AChE in a dose-dependent relationship (Figure 1). Compounds 1 and m demonstrate weak inhibition of AChE compared with compound 6i, suggesting that the presence of 1,3,4-oxadiazole unit improves the activity.
In vitro inhibitory activities of glycosyl oxadiazoles against AChE.
| Compound | Inhibition (%)a | IC50 (μm) |
|---|---|---|
| 1 | 46.2 | – |
| 6a | 47.7 | – |
| 6b | 59.4 | – |
| 6c | 92.1 | 2.6±0.5 |
| 6d | 90.2 | 4.2±0.2 |
| 6e | 55.1 | – |
| 6f | 91.3 | 3.1±0.4 |
| 6g | 68.3 | – |
| 6h | 83.3 | 11.6±0.8 |
| 6i | 96.8 | 1.6±0.3 |
| 6j | 91.1 | 2.7±0.5 |
| mb | 17.3 | – |
| nc | 14.5 | – |
| Tacrine | 0.269±0.004 | |
| Galantamine | 2.67±0.15 |
aThe inhibition activities of the compounds at the concentration of 50 μg/mL. bm stands for 5-(4-(N,N-di-Me)-C6H4)-1,3,4-oxadiazole-2-amine. cn stands for D-glucosamine hydrochloride.
Dose-dependent inhibition of AChE by compound 6i. Values are presented as mean±SD, n=3.
Conclusion
A new series of C2-glycosyl oxadiazole derivatives were designed, synthesized and subjected to biological evaluation. These compounds were characterized by NMR, IR and HRMS. Most of the compounds are active against AChE. Compound 6i shows the best AChE-inhibition activity with an IC50 of 1.61±0.34 μm.
Experimental
Chemistry
All chemicals were purchased from commercial sources and used without further purification. Melting points were determined on a Yanaco melting point apparatus and were uncorrected. IR spectra were recorded on a Bruker Tensor 27 spectrometer in KBr pellets. 1H NMR spectra were recorded on a Bruker Avance 400 MHz at ambient temperature using dimethyl sulfoxide-d6 (DMSO-d6) as a solvent and tetramethylsilane (TMS) as an internal standard. HRMS (ESI) analysis was performed on an Agilent 6230 mass spectrometer. Flash column chromatography was performed on silica 200–300 mesh.
2-Amino-1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranose hydrochloride (1)
A solution of D-glucosamine hydrochloride (10 g, 46.4 mmol) in water (70 mL) at room temperature was stirred and treated with NaOH (1.86 g, 46.5 mmol), and 15 min later dropwise with p-methoxybenzaldehyde (5.7 mL, 46.6 mmol). The mixture was stirred at ambient temperature for an additional 24 h, after which time the resulting white solid was filtered and washed with 500 mL of water to afford 2-(4-methoxy benzylidene)-2-deoxy-β-D-glucopyranose (11.4 g, 83%). A mixture of this product and BnBr (14 mL, 118 mmol) in dimethylformamide (DMF) (50 mL) at 0°C was treated portion-wise with NaH (60%, 5 g, 125 mmol). The mixture was stirred at room temperature for 12 h, then diluted with a large amount of water and extracted with CH2Cl2 (3×50 mL). The extract was concentrated under reduced pressure to give a yellow viscous liquid. The solution of the yellow liquid in acetone (100 mL) was treated with hydrochloric acid (7 mL, 5 N) to afford a white solid of 1 after reflux for 1 h. Product 1 was washed with acetone; yield 7.9 g (62%).
2-Isothiocyanato-1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranose (3)
A solution of 1,3,4,6-tetra-O-benzyl-β-D-glucosamine hydrochloride 1 (1 mmol) and triethylamine (3 mmol) in acetonitrile (15 mL) was cooled in an ice bath and treated dropwise with carbon disulfide (1 mmol). The mixture was stirred for 2 h, then treated with p-TsCl (1 mmol) and stirred for another 0.5 h on the ice bath. The precipitate of product 3 was crystallized from ethanol; yield 90% of white amorphous powder; mp 55–56°C; IR: 3433, 3030, 2873, 2078, 1454, 1359, 1313, 1068 cm−1; 1H NMR: δ 7.45–7.25 (m, 18H, ArH), 7.24–7.17 (dd, J=7 Hz, 2H, ArH), 4.81 (dd, J=16, 10 Hz, 4H, PhCH2, HGlu), 4.73–4.62 (m, 2H, PhCH2), 4.61–4.48 (m, 3H, PhCH2), 3.95–3.87 (m, 2H, HGlu), 3.67 (ddd, J=14, 12, 7 Hz, 3H, HGlu), 3.54 (dd, J=12, 7 Hz, 1H, HGlu); ESI-HRMS (m/z): Calcd for C35H35NNaO5S [M+Na]+: 604.2128; found: 604.2130.
General procedure for the preparation of N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-aryl-1,3,4-oxadiazole-2-amines 6a–j
Glycosyl isothiocyanate 3 (0.58 g, 1 mmol) was added in one portion to a stirred solution of hydrazide 4 (1 mmol) in MeCN (10 mL). The reaction mixture was heated under reflux for 3–4 h, and then the solvent was eliminated under reduced pressure. The residue was crystallized from aqueous ethanol to obtain the desired product 5a–j. p-TsCl (0.21 g, 1.1 mmol) was added to a stirred solution of acylthiosemicarbazide 5 (1 mmol) and triethylamine (0.16 mL, 2.0 mmol) in MeCN (10 mL). The mixture was stirred for about 2–3 h at 81°C, and the reaction progress was monitored by thin-layer chromatography (TLC). The desired compound 6a–j was purified by column chromatography on silica gel eluting with ethyl acetate/petroleum ether (1:2) to give a white amorphous product.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-phenyl-1,3,4-oxadiazole-2-amine (6a)
Yield 86%; mp 166–168°C; IR (cm−1): 3421, 3226, 3060, 2924, 1630, 1496, 1453, 1397, 1116, 1064; 1H NMR: δ 8.15 (d, J=9 Hz, 1H, NH), 7.86–7.80 (m, 2H, ArH), 7.56–7.50 (m, 3H, ArH), 7.40–7.27 (m, 8H, ArH), 7.25–7.12 (m, 12H, ArH), 4.82 (d, J=12 Hz, 1H, H-1Glu), 4.80–4.65 (m, 4H, PhCH2), 4.62–4.51 (m, 4H, PhCH2), 3.85–3.69 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.65–3.50 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C42H41N3NaO6 [M+Na]+: 706.2888; found: 706.2890.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-methylphenyl)-1,3,4-oxadiazole-2-amine (6b)
Yield 88%; mp 159–160°C; IR (cm−1): 3446, 3170, 2923, 1629, 1400, 1071, 1028; 1H NMR: δ 8.08 (d, J=9 Hz, 1H, NH), 7.71 (d, J=8 Hz, 2H, ArH), 7.42–7.27 (m, 10H, ArH), 7.25–7.13 (m, 12H, ArH), 4.82 (d, J=12 Hz, 1H, H-1Glu), 4.78–4.70 (m, 3H, PhCH2), 4.68–4.52 (m, 5H, PhCH2), 3.83–3.68 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.63–3.52 (m, 3H, H-5Glu, H-3Glu, H-2Glu), 2.40–2.32 (s, 3H, CH3); ESI-HRMS (m/z): Calcd for C43H43N3NaO6 [M+Na]+: 720.3044; found: 720.3046.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(2-thienyl)-1,3,4-oxadiazole-2-amine (6c)
Yield 84%; mp 147–148°C; IR (cm−1): 3420, 3201, 3026, 2923, 1496, 1468, 1400, 1114, 1066; 1H NMR: δ 8.36 (d, J=9 Hz, 1H, NH), 7.66 (d, J=8 Hz, 1H, ArH), 7.42 (d, J=4 Hz, 1H, ArH), 7.40–7.29 (m, 8H, ArH), 7.27–7.11 (m, 13H, ArH), 4.82 (d, J=12.5 Hz, 1H, H-1Glu), 4.76–4.65 (m, 4H, PhCH2), 4.63–4.52 (m, 4H, PhCH2), 3.86 (t, J=8 Hz, 1H, H-4Glu), 3.78–3.67 (m, 2H, H-6aGlu, H-6bGlu), 3.61–3.50 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C40H39N3NaO6S [M+Na]+: 712.2452; found: 712.2456.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-pyridyl)-1,3,4-oxadiazole-2-amine (6d)
Yield 86%; mp 182–183°C; IR (cm−1): 3421, 3230, 3060, 2924, 1627, 1465, 1398, 1061, 1028; 1H NMR: δ 8.98 (d, J=2 Hz, 1H, ArH), 8.70 (dd, J=5, 2 Hz, 1H, ArH), 8.26 (d, J=9 Hz, 1H, NH), 8.16 (2t, J=2 Hz, 1H, ArH), 7.56 (dd, J=8.5 Hz, 1H, ArH), 7.40–7.27 (m, 8H, ArH), 7.25–7.10 (m, 12H, ArH), 4.82 (d, J=12 Hz, 1H, H-1Glu), 4.79–4.64 (m, 4H, PhCH2), 4.62–4.52 (m, 4H, PhCH2), 3.84–3.69 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.65–3.55 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C41H40N4NaO6 [M+Na]+: 707.2840; found: 707.2843.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole-2-amine (6e)
Yield 90%; mp 147–148°C; IR (cm−1): 3426, 3174, 3028, 2926, 1598, 1497, 1453, 1400, 1216, 1125, 1069, 1043; 1H NMR: (δ 8.37 (d, J=9 Hz, 1H, NH), 7.43–7.27 (m, 12H, ArH), 7.25–7.15 (m, 11H, ArH), 7.05–7.01 (m, 1H, ArH), 4.83 (d, J=12.5 Hz, 1H, H-1Glu), 4.78–4.67 (m, 4H, PhCH2), 4.64–4.51 (m, 4H, PhCH2), 3.87 (t, J=8 Hz, 1H, H-4Glu), 3.82 (s, 3H, OCH3), 3.77–3.68 (m, 2H, H-6aGlu, H-6bGlu), 3.61–3.51 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C43H43N3NaO7 [M+Na]+: 736.2993; found: 736.2998.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(2-chlorophenyl)-1,3,4-oxadiazole-2-amine (6f)
Yield 83%; mp 121–122°C; IR (cm−1): 3421, 3231, 3062, 2924, 1627, 1508, 1454, 1397, 1362, 1149, 1076, 1028; 1H NMR: δ 8.25 (d, J=9 Hz, 1H, NH), 7.78 (dd, J=8, 1.8 Hz, 1H, ArH), 7.65 (dd, J=8, 1.1 Hz, 1H, ArH), 7.58–7.47 (m, 2H, ArH), 7.40–7.27 (m, 8H, ArH), 7.26–7.13 (m, 12H, ArH), 4.83 (d, J=12.5 Hz, 1H, H-1Glu), 4.79–4.63 (m, 4H, PhCH2), 4.62–4.51 (m, 4H, PhCH2), 3.84–3.68 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.63–3.50 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C42H40ClN3NaO6 [M+Na]+: 740.2498; found: 740.2501.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-hydroxylphenyl)-1,3,4-oxadiazole-2-amine (6g)
Yield 86%; mp 181–182°C; IR (cm−1): 3421, 3142, 3030, 2956, 1650, 1611, 1497, 1398, 1279, 1173, 1072, 1027; 1H NMR: δ 10.10 (s, 1H, OH), 7.98 (d, J=9 Hz, 1H, NH), 7.66 (t, J=9 Hz, 2H, ArH), 7.41–7.12 (m, 20H, ArH), 6.89 (d, J=9 Hz, 2H, ArH), 4.81 (d, J=12 Hz, 1H, H-1Glu), 4.78–4.50 (m, 8H, PhCH2), 3.83–3.68 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.69–3.50 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C42H41N3NaO7 [M+Na]+: 722.2837; found: 722.2838.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-iodinylphenyl)-1,3,4-oxadiazole-2-amine (6h)
Yield 82%; mp 176–177°C; IR (cm−1): 3446, 3229, 3059, 2922, 1627, 1478, 1453, 1397, 1362, 1203, 1055, 1005; 1H NMR: δ 8.19 (d, J=9 Hz, 1H, NH), 7.90 (d, J=8.5 Hz, 2H, ArH), 7.58 (d, J=8.5 Hz, 2H, ArH), 7.40–7.27 (m, 8H, ArH), 7.25–7.10 (m, 12H, ArH), 4.81 (d, J=12 Hz, 1H, H-1Glu), 4.77–4.61 (m, 4H, PhCH2), 4.60–4.50 (m, 4H, PhCH2), 3.83–3.67 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.64–3.51 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C42H40IN3NaO6 [M+Na]+: 832.1854; found: 832.1860.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole-2-amine (6i)
Yield 88%; mp 156–157°C; IR (cm−1): 3425, 3179, 3029, 2923, 1601, 1518, 1498, 1400, 1219, 1124, 1070; 1H NMR: δ 8.34 (d, J=9 Hz, 1H, NH), 7.84–7.77 (m, 2H, ArH), 7.41–7.26 (m, 11H, ArH), 7.25–7.13 (m, 11H, ArH), 4.82 (d, J=12.5 Hz, 1H, H-1Glu), 4.76–4.66 (m, 4H, PhCH2), 4.63–4.51 (m, 4H, PhCH2), 3.86 (t, J=8 Hz, 1H, H-4Glu), 3.78–3.67 (m, 2H, H-6aGlu, H-6bGlu), 3.62–3.52 (m, 3H, H-5Glu, H-3Glu, H-2Glu); ESI-HRMS (m/z): Calcd for C42H40FN3NaO6 [M+Na]+: 724.2793; found: 724.2796.
N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-dimethylaminophenyl)-1,3,4-oxadiazole-2-amine (6j)
Yield 83%; mp 123–124°C; IR (cm−1): 3422, 3234, 3060, 2906, 1633, 1614, 1519, 1397, 1197, 1068, 1028; 1H NMR: δ 7.89 (d, J=9 Hz, 1H, NH), 7.62 (d, J=9 Hz, 2H, ArH), 7.41–7.25 (m, 8H, ArH), 7.24–7.15 (m, 12H, ArH), 6.80 (d, J=9 Hz, 2H, ArH), 4.81 (d, J=12.5 Hz, 1H, H-1Glu), 4.78–4.62 (m, 4H, PhCH2), 4.60–4.51 (m, 4H, PhCH2), 3.83–3.66 (m, 3H, H-4Glu, H-6aGlu, H-6bGlu), 3.63–3.49 (m, 3H, H-5Glu, H-3Glu, H-2Glu), 2.98 (s, 6H, CH3); ESI-HRMS (m/z): Calcd for C44H46N4NaO6 [M+Na]+: 749.3310; found: 749.3312.
In vitro cholinesterase activity assay
AChE, acetylthiocholine iodide (ATCI), 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB), galantamine and tacrine were purchased from Sigma-Aldrich. AChE activities were measured using Ellman’s colorimetric method with a slight modification [39]; galantamine and tacrine were the reference compounds. For the determination, a 96-well plate was used as the carrier. First, 130 μL of buffer solution, 20 μL of AChE solution, 20 μL of color developer and 10 μL of methanol were added to the first column of the 96-well plate as a control blank system. Then, 130 μL of buffer solution, 20 μL of AChE solution, 20 μL of developer and 10 μL of the analyte solution were added. After all samples were added, the plate was treated with 20 μL of substrate and shaken evenly. The plate was quickly placed in the microplate reader and the temperature was maintained at 20–25°C. The reaction rates were compared and the percent inhibition due to the presence of tested compounds was calculated. All samples were assayed in triplicate. The 50% inhibitory concentration (IC50) was calculated from a dose-response curve obtained by plotting the percentage of inhibition versus the log concentration with the use of the Origin 8.0 software. The results were described as mean±standard deviation (SD).
Acknowledgments
This work was supported by the Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX17-2074), Natural Science Foundation of Jiangsu Province (BK20151281), Open-end Funds of Jiangsu Key Laboratory of Marine Biotechnology (HS2014007) and Public Science and Technology Research Funds Projects of Ocean (201505023).
References
[1] Tsvetkov, Y. E.; Burg-Roderfeld, M.; Loers, G.; Ardá, A.; Sukhova, E. V.; Khatuntseva, E. A.; Jiménez-Barbero, J. Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. The specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and STD NMR. J. Am. Chem. Soc.2011, 134, 426–435.10.1021/ja2083015Search in Google Scholar PubMed
[2] Kimura, M.; Masui, Y.; Shirai, Y.; Honda, C.; Moriwaki, K.; Imai, T.; Nakano, H. Preparation of branched cyclomaltoheptaose with 3-O-α-L-fucopyranosyl-α-D-mannopyranose and changes in fucosylation of HCT116 cells treated with the fucose-modified cyclomaltoheptaose. Carbohydr. Res.2013, 374, 49–58.10.1016/j.carres.2013.03.022Search in Google Scholar PubMed
[3] Delbianco, M.; Bharate, P.; Varela-Aramburu, S.; Seeberger, P. H. Carbohydrates in supramolecular chemistry. Chem. Rev. 2016, 116, 1693–1752.10.1021/acs.chemrev.5b00516Search in Google Scholar PubMed
[4] Ernst, B.; Magnani, J. L. From carbohydrate leads to glycomimetic drugs. Nat. Rev. Drug Discov. 2009, 8, 661–677.10.1038/nrd2852Search in Google Scholar PubMed PubMed Central
[5] Bertozzi, C. R.; Kiessling, L. L. Chemical glycobiology. Science2001, 291, 2357–2364.10.1126/science.1059820Search in Google Scholar PubMed
[6] Xie, J. Synthesis of new sugar amino acid derivatives of D-glucosamine. Carbohydr. Res. 2003, 338, 399–405.10.1016/S0008-6215(02)00487-1Search in Google Scholar
[7] Xu, C.; Hall, R.; Cummings, J.; Raushel, F. M. Tight binding inhibitors of N-acyl amino sugar and N-acyl amino acid deacetylases. J. Am. Chem. Soc.2006, 128, 4244–4245.10.1021/ja0600680Search in Google Scholar PubMed
[8] Fu, M.; Qin, C.; Li, W.; Yan, Y.; Zeng, L.; Yang, X. Effect of glucosamine and chitooligomer on the toxicity of arsenite against Escherichia coli. Carbohyd. Polym. 2013, 91, 390–396.10.1016/j.carbpol.2012.08.065Search in Google Scholar PubMed
[9] Terencio, M. C.; Ferrándiz, M. L.; Carceller, M. C.; Ruhí, R.; Dalmau, P.; Vergés, J.; Alcaraz, M. J. Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats. Biomed. Pharmacother. 2016, 79, 120–128.10.1016/j.biopha.2016.02.005Search in Google Scholar PubMed
[10] Nagaoka, I.; Igarashi, M.; Hua, J.; Ju, Y.; Yomogida, S.; Sakamoto, K. Recent aspects of the anti-inflammatory actions of glucosamine. Carbohyd. Polym. 2011, 84, 825–831.10.1016/j.carbpol.2010.04.007Search in Google Scholar
[11] Oh, H. J.; Lee, J. S.; Song, D. K.; Shin, D. H.; Jang, B. C.; Suh, S. I.; Baek, W. K. D-glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K. Biochem. Bioph. Res. Commun.2007, 360, 840–846.10.1016/j.bbrc.2007.06.137Search in Google Scholar PubMed
[12] Blagodatskikh, I. V.; Kulikov, S. N.; Vyshivannaya, O. V.; Bezrodnykh, E. A.; Yamskov, I. A.; Tikhonov, V. E. Influence of glucosamine on oligochitosan solubility and antibacterial activity. Carbohydr. Res. 2013, 381, 28–32.10.1016/j.carres.2013.08.012Search in Google Scholar PubMed
[13] Quastel, J. Inhibition of tumour growth by D-glucosamine. Nature1953, 171, 252–254.10.1038/171252a0Search in Google Scholar PubMed
[14] Xing, R.; Liu, S.; Guo, Z.; Yu, H.; Li, C.; Ji, X.; Feng, J.; Li, P. The antioxidant activity of glucosamine hydrochloride in vitro. Bioorg. Med. Chem. 2006, 14, 1706–1709.10.1016/j.bmc.2005.10.018Search in Google Scholar PubMed
[15] Liu, W. W.; Li, Q. X.; Shi, D. H. Synthesis, characterization, and biological evaluation of some novel glycosyl 1,3,4-thiadiazole derivatives as acetylcholinesterase inhibitors. Heterocycles2015, 91, 275–286.10.3987/COM-14-13134Search in Google Scholar
[16] Punganuru, S. R.; Mostofa, A. G. M.; Madala, H. R.; Basak, D.; Srivenugopal, K. S. Potent anti-proliferative actions of a non-diuretic glucosamine derivative of ethacrynic acid. Bioorg. Med. Chem. Lett. 2016, 26, 2829–2835.10.1016/j.bmcl.2016.04.062Search in Google Scholar PubMed
[17] Garifullin, B. F.; Strobykina, I. Y.; Sharipova, R. R.; Kravchenko, M. A.; Andreeva, O. V.; Bazanova, O. B.; Kataev, V. E. Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol. Carbohydr. Res.2016, 431, 15–21.10.1016/j.carres.2016.05.007Search in Google Scholar PubMed
[18] Yang, J.; Li, J. R.; Yang, J. X.; Li, L. L.; Ouyang, W. J.; Wu, S. W.; Zhang, F. Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine. Chinese Chem. Lett. 2014, 25, 1052–1058.10.1016/j.cclet.2014.05.030Search in Google Scholar
[19] Mendis, E.; Kim, M. M.; Rajapakse, N.; Kim, S. K. The inhibitory mechanism of a novel cationic glucosamine derivative against MMP-2 and MMP-9 expressions. Bioorg. Med. Chem. Lett. 2009, 19, 2755–2760.10.1016/j.bmcl.2009.03.126Search in Google Scholar PubMed
[20] Shen, C.; Shen, H.; Yang, M.; Xia, C.; Zhang, P. A novel D-glucosamine-derived pyridyl-triazole for solvent-free Mizoroki–Heck reactions and its application in the synthesis of Axitinib. Green Chem. 2015, 17, 225–230.10.1039/C4GC01606HSearch in Google Scholar
[21] Bepary, S.; Yoon, I. K.; Lee, G. H. Novel 3-amino-7-(aminomethyl)-1H-indazol-4-ol as the PI3Kγ enzyme inhibitor. Bull. Korean. Chem. Soc. 2016, 37, 2054–2057.10.1002/bkcs.10994Search in Google Scholar
[22] Dighe, S. U.; Khan, S.; Soni, I.; Jain, P.; Shukla, S.; Yadav, R.; Sen, P.; Meeran, S. M.; Batra, S. Synthesis of β-carboline-based N-heterocyclic carbenes and their antiproliferative and antimetastatic activities against human breast cancer cells. J. Med. Chem. 2015, 58, 3485–3499.10.1021/acs.jmedchem.5b00016Search in Google Scholar PubMed
[23] Chen, Y.; Yu, K.; Tan, N. Y.; Qiu, R. H.; Liu, W.; Luo, N. L.; Yin, S. F. Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds. Eur. J. Med. Chem. 2014, 79, 391–398.10.1016/j.ejmech.2014.04.026Search in Google Scholar PubMed
[24] Mathew, V.; Keshavayya, J.; Vaidya, V. P. Heterocyclic system containing bridgehead nitrogen atom: synthesis and pharmacological activities of some substituted 1,2,4-triazolo [3,4-b]-1,3,4-thiadiazoles. Eur. J. Med. Chem.2006, 41, 1048–1055.10.1016/j.ejmech.2006.03.018Search in Google Scholar PubMed
[25] Borg, S.; Estenne-Bouhtou, G.; Luthman, K.; Csoeregh, I.; Hesselink, W.; Hacksell, U. Synthesis of 1,2,4-oxadiazole-, 1,3,4-oxadiazole- and 1,2,4-triazole-derived dipeptidomimetics. J. Org. Chem. 1995, 60, 3112–3117.10.1021/jo00115a029Search in Google Scholar
[26] Li, P.; Yin, J.; Xu, W.; Wu, J.; He, M.; Hu, D.; Song, B. Synthesis, antibacterial activities, and 3D-QSAR of sulfone derivatives containing 1,3,4-oxadiazole moiety. Chem. Biol. Drug Des. 2013, 82, 546–551.10.1111/cbdd.12181Search in Google Scholar PubMed
[27] Padmaja, A.; Pedamalakondaiah, D.; Sravya, G.; Reddy, G. M.; Kumar, M. V. J. Synthesis and antioxidant activity of a new class of sulfone/sulfonamide-linked bis(oxadiazoles), bis(thiadiazoles), and bis(triazoles). J. Med. Chem. Res.2015, 24, 2011–2020.10.1007/s00044-014-1277-5Search in Google Scholar
[28] Wu, W.; Chen, Q.; Tai, A.; Jiang, G.; Ouyang, G. Synthesis and antiviral activity of 2-substituted methylthio-5-(4-amino-2-methylpyrimidin-5-yl)-1,3,4-oxadiazole derivatives. Bioorg. Med. Chem. Lett.2015, 25, 2243–2250.10.1016/j.bmcl.2015.02.069Search in Google Scholar PubMed
[29] Zhang, M. Z.; Mulholland, N.; Beattie, D.; Irwin, D.; Gu, Y. C.; Chen, Q.; Clough, J. Synthesis and antifungal activity of 3-(1,3,4-oxadiazol-5-yl)indoles and 3-(1,3,4-oxadiazol-5-yl)methylindoles. Eur. J. Med. Chem.2013, 63, 22–28.10.1016/j.ejmech.2013.01.038Search in Google Scholar PubMed
[30] Dekhane, D. V.; Pawar, S. S.; Gupta, S.; Shingare, M. S.; Patil, C. R.; Thore, S. N. Synthesis and anti-inflammatory activity of some new 4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted heteroazole derivatives. Bioorg. Med. Chem. Lett.2011, 21, 6527–6531.10.1016/j.bmcl.2011.08.061Search in Google Scholar PubMed
[31] Zhang, Y.; Liu, X. H.; Zhan, Y. Z.; Zhang, L. Y.; Li, Z. M.; Li, Y. H.; Wang, B. L. Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors. Bioorg. Med. Chem. Lett.2016, 26, 4661–4667.10.1016/j.bmcl.2016.08.059Search in Google Scholar PubMed
[32] Distinto, S.; Meleddu, R.; Yanez, M.; Cirilli, R.; Bianco, G.; Sanna, M. L.; Ortuso, F. Drug design, synthesis, in vitro and in silico evaluation of selective monoaminoxidase B inhibitors based on 3-acetyl-2-dichlorophenyl-5-aryl-2,3-dihydro-1,3,4-oxadiazole chemical scaffold. Eur. J. Med. Chem.2016, 108, 542–548.10.1016/j.ejmech.2015.12.026Search in Google Scholar PubMed
[33] Ke, S.; Li, Z.; Qian, X. 1,3,4-Oxadiazole-3(2H)-carboxamide derivatives as potential novel class of monoamine oxidase (MAO) inhibitors: synthesis, evaluation, and role of urea moiety. Bioorg. Med. Chem. 2008, 16, 7565–7572.10.1016/j.bmc.2008.07.026Search in Google Scholar PubMed
[34] Mazouz, F.; Lebreton, L.; Milcent, R.; Burstein, C. 5-Aryl-1,3,4-oxadiazol-2 (3H)-one derivatives and sulfur analogues as new selective and competitive monoamine oxidase type B inhibitors. Eur. J. Med. Chem.1990, 25, 659–663.10.1016/0223-5234(90)90131-LSearch in Google Scholar
[35] Raza, R.; Saeed, A.; Arif, M.; Mahmood, S.; Muddassar, M.; Raza, A.; Iqbal, J. Synthesis and biological evaluation of 3-thiazolocoumarinyl Schiff-base derivatives as cholinesterase inhibitors. Chem. Biol. Drug Des.2012, 80, 605–615.10.1111/j.1747-0285.2012.01435.xSearch in Google Scholar PubMed
[36] Wei, H.; Ruan, J.; Zhang, X. Coumarin–chalcone hybrids: promising agents with diverse pharmacological properties. RSC Adv. 2016, 6, 10846–10851.10.1039/C5RA26294ASearch in Google Scholar
[37] Havrylyuk, D.; Roman, O.; Lesyk, R. Synthetic approaches, structure activity relationship and biological applications for pharmacologically attractive pyrazole/pyrazoline–thiazolidine-based hybrids. Eur. J. Med. Chem. 2016, 113, 145–150.10.1016/j.ejmech.2016.02.030Search in Google Scholar PubMed PubMed Central
[38] Cheng, F. C.; Yin, L.; Liu, W. W.; Li, Q. X.; Tang, L. J.; Shi, D. H.; Cao, Z. L. Expedient synthesis of novel glycosyl thiazole derivatives. Heterocycles2015, 91, 2113–2125.10.3987/COM-15-13310Search in Google Scholar
[39] Tao, C. Z.; Liu, F.; Liu, W. W.; Zhu, Y. M.; Li, Y. F.; Liu, X. L.; Zhao, J. Synthesis of N-aryl-D-glucosamines through copper-catalyzed C–N coupling. Tetrahedron Lett. 2012, 53, 7093–7096.10.1016/j.tetlet.2012.10.069Search in Google Scholar
[40] Ellman, G. L.; Courtney, K. D.; Andres Jr, V.; Featherstone, R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88–95.10.1016/0006-2952(61)90145-9Search in Google Scholar PubMed
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