Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry and HPLC Enantioseparation
2.2. hMAO-A and hMAO-B Inhibition Studies
2.3. Docking Studies
3. Materials and Methods
3.1. General
3.2. General Synthesis for Acetophenone Derivatives A3–A8
3.2.1. General Synthesis and Characterization Data for Chalcones C1–C18
3.2.2. Synthesis and Characterization Data for 3,5-disubstituted-N-thiocarbamoylated Pyrazolines P1–P6
3.2.3. Synthesis and Characterization Data for 3,5-disubstituted-N-acetylated Pyrazolines P7–P18
3.3. hMAO-A and hMAO-B Inhibition Studies
3.4. Enantioselective HPLC
3.5. Molecular Modeling Studies
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | Structure | IC50 (µM ± SD) a | SI b | |
---|---|---|---|---|
hMAO-A | hMAO-B | |||
(S)-P1 | 46.6 ± 2.62 | >100 | <0.47 | |
(R)-P1 | 50.6 ± 2.67 | >100 | <0.51 | |
(S)-P2 | 32.3 ± 4.46 | >100 | <0.32 | |
(R)-P2 | 33.9 ± 1.29 | >100 | <0.34 | |
(S)-P3 | 9.59 ± 0.83 | 42.5 ± 2.61 | 0.23 | |
(R)-P3 | 8.00 ± 0.83 | 2.77 ± 0.39 | 2.89 | |
(S)-P4 | 39.2 ± 2.15 | 5.03 ± 0.88 | 7.78 | |
(R)-P4 | 3.63 ± 0.50 | 0.38 ± 0.06 | 9.55 | |
(S)-P5 | 55.2 ± 2.72 | 2.79 ± 0.87 | 19.77 | |
(R)-P5 | 3.03 ± 0.60 | 0.44 ± 0.028 | 6.89 | |
P6 | >100 | 54.1 ± 7.54 | >1.85 | |
P7 | 39.3 ± 5.94 | 14.5 ± 2.78 | 2.72 | |
P8 | >100 | 2.29 ± 0.42 | >43.67 | |
P9 | 9.13 ± 0.34 | 27.3 ± 0.57 | 0.33 | |
P10 | 86.8 ± 14.7 | 3.22 ± 0.48 | 26.96 | |
P11 | >100 | 12.2 ± 0.71 | >8.19 | |
P12 | 80.6 ± 10.0 | >100 | <0.81 | |
P13 | 5.74 ± 1.66 | 3.11 ± 0.66 | 1.85 | |
P14 | 4.13 ± 0.26 | 1.08 ± 0.05 | 3.82 | |
P15 | 12.1 ± 0.14 | 11.0 ± 3.56 | 1.11 | |
P16 | >100 | >100 | \ | |
P17 | >100 | >100 | \ | |
P18 | >100 | >100 | \ | |
Toloxatone | 3.92 ± 0.15 c | - | - | |
Lazabemide | - | 0.091 ± 0.15 c | - |
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Guglielmi, P.; Carradori, S.; Poli, G.; Secci, D.; Cirilli, R.; Rotondi, G.; Chimenti, P.; Petzer, A.; Petzer, J.P. Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles. Molecules 2019, 24, 484. https://doi.org/10.3390/molecules24030484
Guglielmi P, Carradori S, Poli G, Secci D, Cirilli R, Rotondi G, Chimenti P, Petzer A, Petzer JP. Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles. Molecules. 2019; 24(3):484. https://doi.org/10.3390/molecules24030484
Chicago/Turabian StyleGuglielmi, Paolo, Simone Carradori, Giulio Poli, Daniela Secci, Roberto Cirilli, Giulia Rotondi, Paola Chimenti, Anél Petzer, and Jacobus P. Petzer. 2019. "Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles" Molecules 24, no. 3: 484. https://doi.org/10.3390/molecules24030484