Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Anticholinesterase Activity Assay
2.3. Enzyme Kinetic Studies
2.4. Molecular Docking Studies
3. Materials and Methods
3.1. Chemistry
3.1.1. 5(6)-Chloro/fluoro-2-((4-methylcarboxylate)phenyl)-1H-benzimidazole
3.1.2. 4-(5(6)-Chloro/fluoro-1H-benzimidazol-2-yl)benzohydrazide
3.1.3. N-methyl/ethyl-2-[4-(5(6)-chloro/fluoro-1H-benzimidazol-2-yl)benzoyl]hydrazine-1-carbothioamide
3.1.4. 4-Methyl/Ethyl-5[4-5(6)-chloro/fluoro-1H-benzimidazol-2-yl)phenyl)-4H-1,2,4-triazole-3-thiol (1a–d)
3.1.5. 2-(4-(4-Methyl/ethyl-5-(2-(substitutedphenyl)-2-oxo-ethylthio)-4H-1,2,4-triazol-3yl)-phenyl)-5(6)-chloro/fluoro-1H-benzimidazoles 3a–p
3.2. Anticholinesterase Activity Assay
3.3. Kinetic Studies of Enzyme Inhibition
3.4. Molecular Docking Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 3a–p are available from the authors. |
Compounds | R1 | R2 | R3 | R4 | Yield (%) |
---|---|---|---|---|---|
1a | –Cl | –CH3 | - | - | 81 |
1b | –Cl | –C2H5 | - | - | 78 |
1d | –F | –CH3 | - | - | 77 |
1c | –F | –C2H5 | - | - | 75 |
3a | –Cl | –CH3 | –H | –CN | 84 |
3b | –Cl | –CH3 | –H | –Br | 82 |
3c | –Cl | –CH3 | –H | –CH3 | 79 |
3d | –Cl | –CH3 | –OH | –OH | 76 |
3e | –Cl | –C2H5 | –H | –CN | 81 |
3f | –Cl | –C2H5 | –H | –Br | 80 |
3g | –Cl | –C2H5 | –H | –CH3 | 74 |
3h | –Cl | –C2H5 | –OH | –OH | 83 |
3i | –F | –CH3 | –H | –CN | 76 |
3j | –F | –CH3 | –H | –Br | 73 |
3k | –F | –CH3 | –H | –CH3 | 71 |
3l | –F | –CH3 | –OH | –OH | 77 |
3m | –F | –C2H5 | –H | –CN | 70 |
3n | –F | –C2H5 | –H | –Br | 73 |
3o | –F | –C2H5 | –H | –CH3 | 82 |
3p | –F | –C2H5 | –OH | –OH | 81 |
Compounds | % Inhibition | |||
---|---|---|---|---|
AChE | BChE | |||
10−3 M | 10−4 M | 10−3 M | 10−4 M | |
3a | 68.18 ± 1.05 | 47.26 ± 0.62 | 40.28 ± 0.98 | 25.13 ± 0.56 |
3b | 44.20 ± 0.87 | 26.18 ± 0.63 | 28.15 ± 0.97 | 18.42 ± 0.88 |
3c | 39.18 ± 0.71 | 17.89 ± 0.54 | 26.11 ± 0.74 | 20.21 ± 0.61 |
3d | 98.55 ± 1.17 | 93.99 ± 1.10 | 51.19 ± 0.99 | 38.12 ± 0.41 |
3e | 77.29 ± 1.06 | 41.22 ± 0.84 | 38.22 ± 0.63 | 22.41 ± 0.47 |
3f | 47.22 ± 0.67 | 24.08 ± 0.48 | 29.15 ± 0.59 | 17.88 ± 0.40 |
3g | 37.20 ± 0.68 | 18.33 ± 0.38 | 31.89 ± 0.99 | 24.75 ± 0.95 |
3h | 98.25 ± 1.12 | 94.55 ± 1.08 | 61.26 ± 0.90 | 35.20 ± 0.42 |
3i | 61.22 ± 1.02 | 38.28 ± 0.67 | 43.51 ± 0.78 | 18.49 ± 0.50 |
3j | 48.51 ± 0.88 | 18.39 ± 0.60 | 29.64 ± 0.87 | 21.44 ± 0.70 |
3k | 42.29 ± 0.71 | 27.88 ± 0.67 | 36.17 ± 0.93 | 21.16 ± 0.97 |
3l | 94.58 ± 1.74 | 83.20 ± 1.13 | 55.43 ± 0.47 | 29.88 ± 0.38 |
3m | 59.03 ± 0.88 | 39.26 ± 0.46 | 48.11 ± 0.38 | 20.66 ± 0.45 |
3n | 49.27 ± 0.55 | 30.21 ± 0.49 | 27.10 ± 0.53 | 18.77 ± 0.42 |
3o | 28.06 ± 0.33 | 19.22 ± 0.30 | 25.99 ± 0.38 | 20.08 ± 0.46 |
3p | 87.26 ± 1.17 | 81.25 ± 1.88 | 53.19 ± 0.46 | 31.44 ± 0.38 |
Donepezil | 99.42 ± 1.85 | 97.26 ± 1.24 | - | - |
Tacrine | - | - | 98.52 ± 1.66 | 95.50 ± 1.74 |
Compounds | % Inhibition of AChE | AChE IC50 (nM) | ||||
---|---|---|---|---|---|---|
10−5 M | 10−6 M | 10−7 M | 10−8 M | 10−9 M | ||
3d | 87.26 ± 1.28 | 78.85 ± 1.19 | 67.18 ± 0.92 | 45.32 ± 0.82 | 15.75 ± 0.48 | 31.9 ± 0.1 |
3h | 90.23 ± 1.03 | 81.25 ± 1.08 | 65.32 ± 0.97 | 44.28 ± 0.71 | 17.20 ± 0.58 | 29.5 ± 1.2 |
3l | 73.18 ± 1.17 | 68.20 ± 0.97 | 48.11 ± 0.61 | 32.29 ± 0.58 | 18.77 ± 0.37 | 169.4 ± 7.2 |
3p | 77.48 ± 1.98 | 71.62 ± 1.08 | 47.83 ± 0.97 | 39.33 ± 0.67 | 15.47 ± 0.64 | 139.9 ± 5.1 |
Donepezil | 94.11 ± 1.71 | 90.17 ± 1.02 | 75.65 ± 1.15 | 35.74 ± 0.58 | 17.89 ± 0.42 | 21.8 ± 0.9 |
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Acar Cevik, U.; Saglik, B.N.; Levent, S.; Osmaniye, D.; Kaya Cavuşoglu, B.; Ozkay, Y.; Kaplancikli, Z.A. Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives. Molecules 2019, 24, 861. https://doi.org/10.3390/molecules24050861
Acar Cevik U, Saglik BN, Levent S, Osmaniye D, Kaya Cavuşoglu B, Ozkay Y, Kaplancikli ZA. Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives. Molecules. 2019; 24(5):861. https://doi.org/10.3390/molecules24050861
Chicago/Turabian StyleAcar Cevik, Ulviye, Begüm Nurpelin Saglik, Serkan Levent, Derya Osmaniye, Betul Kaya Cavuşoglu, Yusuf Ozkay, and Zafer Asim Kaplancikli. 2019. "Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives" Molecules 24, no. 5: 861. https://doi.org/10.3390/molecules24050861
APA StyleAcar Cevik, U., Saglik, B. N., Levent, S., Osmaniye, D., Kaya Cavuşoglu, B., Ozkay, Y., & Kaplancikli, Z. A. (2019). Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives. Molecules, 24(5), 861. https://doi.org/10.3390/molecules24050861