Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Evaluation
2.3. Physicochemical Properties and ADME Profiling
3. Experimental Section
3.1. General Information
3.2. Synthesis
3.2.1. 1-(4-Nitrophenyl)-3-phenyl/substituted phenylurea 2a–e
3.2.2. 1-(4-Aminophenyl)-3-phenyl/substituted phenylurea 3a–e
3.2.3. General Procedure for Preparation of Target Compounds 5a–x
3.2.4. N-Benzylindoline-2,3-diones 7a,b
3.2.5. General Procedure for Preparation of Target Compounds 8a,b
3.3. In Vitro Cytotoxic Activity
3.3.1. Cell Culture
3.3.2. In vitro Cytotoxic Activity
3.3.3. Physicochemical Properties and ADME Profiling
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Compd. | R | R1 | R2 | IC50 (μM) a | |
---|---|---|---|---|---|
MCF-7 | PC-3 | ||||
5a | H | H | - | 19.53 ± 1.05 | NA b |
5b | H | F | - | 17.14 ± 0.66 | NA b |
5c | H | Cl | - | 19.17 ± 1.94 | 20.43 ± 1.51 |
5d | 4-F | H | - | NA b | NA b |
5e | 4-F | F | - | NA b | NA b |
5f | 4-F | Cl | - | 48.99 ± 3.74 | NA b |
5g | 3-CF3 | H | - | 39.53 ± 4.02 | NA b |
5h | 3-CF3 | F | - | NA b | 51.76 ± 4.01 |
5i | 3-CF3 | Cl | - | 97.65 ± 7.39 | NA b |
5j | 3-Cl | H | - | NA b | NA b |
5k | 3-Cl | F | - | 75.92 ± 7.21 | NA b |
5l | 3-Cl | Cl | - | 1.93 ± 0.17 | NA b |
5m | 3-Cl | Me | - | 35.59 ± 3.27 | 73.22 ± 5.07 |
5n | 3-Cl | OMe | - | 9.60 ± 1.08 | 96.00 ± 6.85 |
5o | 4-Cl | H | - | 1.04 ± 0.10 | 83.54 ± 6.32 |
5p | 4-Cl | F | - | 26.02 ± 2.51 | NA b |
5q | 4-Cl | Cl | - | 3.87 ± 0.31 | NA b |
5r | 4-Cl | Me | - | 12.16 ± 1.17 | NA b |
5s | 4-Cl | OMe | - | 43.08 ± 4.22 | 97.00 ± 3.25 |
8a | - | - | H | 28.00 ± 2.93 | 18.40 ± 1.33 |
8b | - | - | F | 4.66 ± 0.42 | 13.79 ± 0.88 |
Dox. | - | - | - | 7.30 ± 0.84 | 0.84 ± 0.079 |
Compd. | H-bond Donor a,# | H-bond Acceptor b,# | Molecular Weight | AlogP d | No. of Rotatable Bonds e | Polar Surface Area f (Å) |
---|---|---|---|---|---|---|
5a | 3 | 6 | 356.4 | 3.200 | 3 | 82.59 |
5b | 3 | 6 | 374.4 | 3.405 | 3 | 82.59 |
5c | 3 | 6 | 390.8 | 3.864 | 3 | 82.59 |
5d | 3 | 6 | 374.4 | 3.405 | 3 | 82.59 |
5e | 3 | 6 | 392.4 | 3.611 | 3 | 82.59 |
5f | 3 | 6 | 408.8 | 4.07 | 3 | 82.59 |
5g | 3 | 6 | 424.4 | 4.142 | 4 | 82.59 |
5h | 3 | 6 | 442.4 | 4.348 | 4 | 82.59 |
5i | 3 | 6 | 458.8 | 4.807 | 4 | 82.59 |
5j | 3 | 6 | 390.8 | 3.864 | 3 | 82.59 |
5k | 3 | 6 | 408.8 | 4.07 | 3 | 82.59 |
5l | 3 | 6 | 425.3 | 4.529 | 3 | 82.59 |
5m | 3 | 6 | 404.8 | 4.351 | 3 | 82.59 |
5n | 3 | 7 | 420.8 | 3.848 | 4 | 91.82 |
5o | 3 | 6 | 390.8 | 3.864 | 3 | 82.59 |
5p | 3 | 6 | 408.8 | 4.07 | 3 | 82.59 |
5q | 3 | 6 | 425.3 | 4.529 | 3 | 82.59 |
5r | 3 | 6 | 404.8 | 4.351 | 3 | 82.59 |
5s | 3 | 7 | 420.8 | 3.848 | 4 | 91.82 |
8a | 2 | 6 | 480.9 | 5.654 * | 5 | 73.8 |
8b | 2 | 6 | 498.9 | 5.859 * | 5 | 73.8 |
Compd. | ADMET Absorption Level a | ADMET Solubility b | ADMET Solubility Level c | ADMET BBB d | ADMET BBB Level d | CYP2D6 Probability | CYP2D6 e |
---|---|---|---|---|---|---|---|
5a | 0 | −4.438 | 2 | −0.500 | 2 | 0.722 | 1 |
5b | 0 | −4.899 | 2 | −0.436 | 2 | 0.594 | 1 |
5c | 0 | −5.299 | 2 | −0.294 | 2 | 0.584 | 1 |
5d | 0 | −4.878 | 2 | −0.436 | 2 | 0.633 | 1 |
5e | 0 | −5.331 | 2 | −0.373 | 2 | 0.584 | 1 |
5f | 0 | −5.732 | 2 | −0.231 | 2 | 0.485 | 0 |
5g | 0 | −6.048 | 1 | −0.208 | 2 | 0.495 | 0 |
5h | 0 | −6.477 | 1 | −0.145 | 2 | 0.465 | 0 |
5i | 0 | −6.877 | 1 | NA | 4 | 0.544 | 1 |
5j | 0 | −5.289 | 2 | −0.294 | 2 | 0.683 | 1 |
5k | 0 | −5.742 | 2 | −0.231 | 2 | 0.504 | 1 |
5l | 0 | −6.143 | 1 | −0.089 | 2 | 0.514 | 1 |
5m | 0 | −5.734 | 2 | −0.144 | 2 | 0.653 | 1 |
5n | 0 | −5.415 | 2 | −0.441 | 2 | 0.683 | 1 |
5o | 0 | −5.279 | 2 | −0.294 | 2 | 0.623 | 1 |
5p | 0 | −5.732 | 2 | −0.231 | 2 | 0.485 | 0 |
5q | 0 | −6.132 | 1 | −0.089 | 2 | 0.504 | 1 |
5r | 0 | −5.723 | 2 | −0.144 | 2 | 0.643 | 1 |
5s | 0 | −5.404 | 2 | −0.441 | 2 | 0.524 | 1 |
8a | 1 | -6.436 | 1 | NA | 4 | 0.712 | 1 |
8b | 1 | -6.737 | 1 | NA | 4 | 0.762 | 1 |
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Eldehna, W.M.; Fares, M.; Ibrahim, H.S.; Alsherbiny, M.A.; Aly, M.H.; Ghabbour, H.A.; Abdel-Aziz, H.A. Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties. Molecules 2016, 21, 762. https://doi.org/10.3390/molecules21060762
Eldehna WM, Fares M, Ibrahim HS, Alsherbiny MA, Aly MH, Ghabbour HA, Abdel-Aziz HA. Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties. Molecules. 2016; 21(6):762. https://doi.org/10.3390/molecules21060762
Chicago/Turabian StyleEldehna, Wagdy M., Mohamed Fares, Hany S. Ibrahim, Muhammad A. Alsherbiny, Mohamed H. Aly, Hazem A. Ghabbour, and Hatem A. Abdel-Aziz. 2016. "Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties" Molecules 21, no. 6: 762. https://doi.org/10.3390/molecules21060762