Efficient Green Synthesis of Hydrazide Derivatives Using L-Proline: Structural Characterization, Anticancer Activity, and Molecular Docking Studies
Abstract
1. Introduction
2. Results and Discussion
2.1. Antitumor Study
2.2. Molecular Docking Study
2.3. In Silico Pharmacokinetic Profile (ADMET)
3. Experimental
3.1. Synthesis of 2-cyano-N’-(2-cyanoacetyl)acetohydrazide (3)
3.2. Reaction of 3 with Aromatic (or Heteroarmatic) Carbonyl Compounds 4a–e, 6a,b, 8, 10, and 12
3.2.1. Method A
3.2.2. Method B
3.3. Cytotoxicity Assay
3.4. Docking Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Compounds | Thermal Method | Grinding Method | ||
---|---|---|---|---|
Time (h) | (%) Yield | Time (min) | (%) Yield | |
5a | 5 | 75 | 25 | 90 |
5b | 4 | 74 | 27 | 89 |
5c | 3 | 79 | 21 | 92 |
5d | 4 | 73 | 26 | 91 |
5e | 3 | 78 | 20 | 89 |
7a | 5 | 72 | 29 | 84 |
7b | 5 | 70 | 30 | 85 |
9 | 4 | 78 | 27 | 91 |
11 | 5 | 77 | 23 | 90 |
13 | 4 | 79 | 28 | 90 |
Entry | Catalyst (mol%) | Time (min) | Temperature (°C) | Yield (%) |
---|---|---|---|---|
1 | 1 | 25 | 25 | 71 |
2 | 3 | 25 | 25 | 83 |
3 a | 5 | 25 | 25 | 90 |
4 | 10 | 25 | 25 | 90 |
State of Catalyst | New Catalyst | Recycled Catalyst | ||||
---|---|---|---|---|---|---|
(1) | (2) | (3) | (4) | (5) | ||
Yield of product 5a | 90 | 87 | 81 | 78 | 74 | 49 |
Tested Compounds | IC50 Values (μM) | Tested Compounds | IC50 Values (μM) |
---|---|---|---|
5a | 3.8 ± 0.7 | 7b | 37.2 ± 4.2 |
5b | 3.2 ± 1.1 | 9 | 9.3 ± 1.7 |
5c | 9.3 ± 1.4 | 11 | 2.5 ± 0.81 |
5d | 8.5 ± 1.3 | 13 | 3.7 ± 1.0 |
5e | 27.0 ± 2.5 | Cisplatin* | 2.43 ± 1.1 |
7a | 35.3 ± 3.1 |
Compounds | Docking Score (kcal/mol) | No. of Hydrogen Bonding | No. of Arene Interaction | Donor Atom | Acceptor Atom |
---|---|---|---|---|---|
5a | −5.75 | 1 (Gly739) 1 (Ile740) 1 (Arg733) 1 (Gly737) | 1 (π-H) [Gly739] | - | O N |
5b | −5.78 | 1 (Ile740) 2 (Gly737) 1 (Gly739) | - | - | O O/N O |
5c | −5.61 | 1 (Ile740) | 1 (π-H) [Leu738] 1 (π-Cation) [Arg801] | N | - |
5d | −5.72 | 1(Gly739) | 1 (π-H) [Gly739] | - | O |
11 | −6.40 | 1 (Ile740) 1 (Leu738) 1 (Arg733) 1 (Arg801) | - | N - - - | - O N N |
CCL | −4.60 | 2 (Ile740) 1 (Gly739) 1 (Leu738) 1 (Arg733) | - | N/- - - - | -/O O O O |
Compounds | Absorption | Distribution | Metabolism | Excretion (Log mL/min/kg) | Toxicity |
---|---|---|---|---|---|
Intestinal Absorption (Human) Numeric (% Absorbed) | VDss (Log L/kg) | AMES Toxicity (Categorical) (Yes/No) | |||
5a | 74.39 | −0.5 | CYP3A4 Substrate and CYP3A4 inhibitor | 0.25 | No |
5b | 65.21 | −0.33 | CYP1A2 inhibitor | 0.13 | No |
5c | 81.9 | −0.51 | CYP3A4 substrate; CYP1A2, CYP2C19, CYP2C9 and CYP3A4 inhibitor | −0.57 | No |
5d | 81.37 | −0.48 | CYP3A4 substrate; CYP2C19, CYP2C9 and CYP3A4 inhibitor | −0.61 | No |
11 | 83.02 | −0.04 | CYP2D6, CYP3A4 substrate; CYP1A2, CYP2C19, CYP2C9, and CYP3A4 inhibitor | 0.76 | No |
Cisplatin * | 92.60 | 0.30 | - | 1.24 | No |
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Gomha, S.M.; Abolibda, T.Z.; Alruwaili, A.H.; Farag, B.; Boraie, W.E.; Al-Hussain, S.A.; Zaki, M.E.A.; Hussein, A.M. Efficient Green Synthesis of Hydrazide Derivatives Using L-Proline: Structural Characterization, Anticancer Activity, and Molecular Docking Studies. Catalysts 2024, 14, 489. https://doi.org/10.3390/catal14080489
Gomha SM, Abolibda TZ, Alruwaili AH, Farag B, Boraie WE, Al-Hussain SA, Zaki MEA, Hussein AM. Efficient Green Synthesis of Hydrazide Derivatives Using L-Proline: Structural Characterization, Anticancer Activity, and Molecular Docking Studies. Catalysts. 2024; 14(8):489. https://doi.org/10.3390/catal14080489
Chicago/Turabian StyleGomha, Sobhi M., Tariq Z. Abolibda, Awatif H. Alruwaili, Basant Farag, Waleed E. Boraie, Sami A. Al-Hussain, Magdi E. A. Zaki, and Ahmed M. Hussein. 2024. "Efficient Green Synthesis of Hydrazide Derivatives Using L-Proline: Structural Characterization, Anticancer Activity, and Molecular Docking Studies" Catalysts 14, no. 8: 489. https://doi.org/10.3390/catal14080489
APA StyleGomha, S. M., Abolibda, T. Z., Alruwaili, A. H., Farag, B., Boraie, W. E., Al-Hussain, S. A., Zaki, M. E. A., & Hussein, A. M. (2024). Efficient Green Synthesis of Hydrazide Derivatives Using L-Proline: Structural Characterization, Anticancer Activity, and Molecular Docking Studies. Catalysts, 14(8), 489. https://doi.org/10.3390/catal14080489