Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antiproliferative Activity
2.3. Antioxidant Activity
3. Materials and Methods
3.1. Chemistry
3.1.1. General Method and Materials
3.1.2. General Procedure (A) Acid-Catalyzed Claisen-Schmidt Condensation
3.1.3. General Procedure (B1) Base-Catalyzed Claisen–Schmidt Condensation (50% aq. KOH)
3.1.4. General Procedure (B2) Base-Catalyzed Claisen–Schmidt Condensation (Piperidine)
3.1.5. Synthesis and Characterization of Compounds 11–14, 17–19
3.2. Antiproliferative Activity Studies
3.2.1. Cell Cultures
3.2.2. MTT Assay
3.3. Antioxidant Activity Studies
3.3.1. DPPH Radical Scavenging Activity
3.3.2. ABTS Radical Scavenging Activity
3.3.3. Ferric Reducing Antioxidant Power (FRAP)
3.3.4. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Comp. | Ar | R1 | R2 | H-2 (J) | H-3 (J) | C-1 | C-2 | C-3 |
---|---|---|---|---|---|---|---|---|
11a | 2-F-Ph | H | H | 7.29 (15.7, 2.3) | 7.91 (15.7, 1.2) | 188.2 | 119.5 | 140.0 |
11b | CH3 | 7.25 (15.7, 2.3) | 7.88 (15.7, 1.4) | 188.1 | 119.4 | 139.3 | ||
11c | OCH3 | 7.33 (15.8, 2.2) | 7.84 (15.7, 0.9) | 188.3 | 120.9 | 138.5 | ||
11d | H | OCH3 | 7.02 (15.4, 2.2) | 7.84 (15.4, 1.5) | 187.4 | 115.7 | 136.8 | |
11e | OCH2CH3 | 7.07 (15.4, 2.3) | 7.88 (15.4, 1.5) | 187.1 | 115.6 | 136.8 | ||
11f | OCH2CH2CH3 | 7.06 (15.4, 2.2) | 7.88 (15.4, 1.5) | 187.3 | 115.7 | 136.9 | ||
11g | OCH(CH3)2 | 7.09 (15.6, 2.3) | 7.87 (15.6, 1.5) | 187.2 | 115.8 | 136.9 | ||
11h | OCH2CH2 CH2CH3 | 7.05 (15.4, 2.2) | 7.86 (15.4, 1.5) | 187.4 | 115.8 | 136.9 | ||
11i | OCH2CH(CH3)2 | 7.06 (15.4, 2.1) | 7.88 (15.4, 1.4) | 187.4 | 115.8 | 137.0 | ||
11j | OCHCH3CH2 OCH3 | 7.09 (15.5, 2.2) | 7.87 (15.5, 1.4) | 187.7 | 116.4 | 137.4 | ||
11k | OCH2CH2OH | 7.08 (15.5, 2.3) | 7.94 (15.5, 1.3) | 187.0 | 115.5 | 136.8 | ||
12a | 4-CF3-Ph | H | H | 7.63 (15.4) | 8.11 (15.4) | 188.2 | 115.1 | 140.3 |
12b | CH3 | 7.63 (15.4) | 8.06 (15.4) | 188.0 | 114.9 | 139.7 | ||
12c | OCH3 | 7.69 (15.4) | 8.02 (15.4) | 188.6 | 117.0 | 139.2 | ||
13a | 2-OH-Ph | H | H | 7.77 (15.2) | 8.21 (15.2) | 193.1 | 113.9 | 140.4 |
13b | CH3 | 7.75 (15.2) | 8.16 (15.2) | 193.0 | 113.9 | 139.7 | ||
13c | OCH3 | 7.82 (15.3) | 8.11 (15.3) | 193.1 | 115.7 | 138.7 | ||
14a | 4-OH-Ph | H | H | 7.64 (15.5) | 7.99 (15.5) | 187.0 | 115.4 | 137.7 |
14b | CH3 | 7.62 (15.5) | 7.94 (15.5) | 187.0 | 115.4 | 137.0 | ||
14c | OCH3 | 7.69 (15.5) | 7.91 (15.5) | 186.9 | 117.0 | 136.1 | ||
17a | 4-OH-Ph | H | 7.55 (15.4) | 7.63 (15.4) | 183.8 | 121.3 | 139.8 | |
17b | CH3 | 7.56 (15.8) | 7.56 (15.8) | 183.3 | 121.2 | 139.8 | ||
17c | OCH3 | 7.57 (15.5) | 7.59 (15.5) | 183.4 | 120.8 | 140.4 | ||
18a | 3,4-diOH-Ph | H | 7.47 (15.5) | 7.54 (15.5) | 183.8 | 121.2 | 140.3 | |
18b | CH3 | 7.47 | 7.47 | 183.3 | 121.1 | 140.4 | ||
18c | OCH3 | 7.50 (15.5) | 7.51 (15.5) | 183.4 | 120.8 | 140.9 | ||
19a | 3-OCH3-4-OH-Ph | H | 7.64 (15.4) | 7.55 (15.4) | 183.1 | 121.4 | 140.2 | |
19b | CH3 | 7.56 (15.6) | 7.55 (15.6) | 183.3 | 121.3 | 140.3 | ||
19c | OCH3 | 7.59 (15.5) | 7.58 (15.5) | 183.3 | 120.9 | 140.9 |
Comp. | Ar | R1 | R2 | Cell Line, IC50 (µM) ± SD | ||||||
---|---|---|---|---|---|---|---|---|---|---|
MDA-MB-231 | HCT116 | Jurkat | Hela | MCF-7 | MCF-10A | Bj-5ta | ||||
11a | 2-F-Ph | H | H | 51.4 ± 3.2 | 31.8 ± 2.1 | 7.6 ± 0.4 | 41.7 ± 0.2 | 37.1 ± 0.4 | 89.1 ± 2.4 | NT |
11b [22] | CH3 | >100 | 41.5 ± 1.7 | 32.4 ± 1.2 | 57.9 ± 0.4 | 47.5 ± 4.3 | >100 | NT | ||
11c [6] | OCH3 | 21.1 ± 3.9 | 37.9 ± 2.7 | 5.9 ± 1.0 | 19.2 ± 5.7 | 20.0 ± 7.9 | 67 ± 2.9 | NT | ||
11d | H | OCH3 | 95.5 ± 2.7 | 45.5 ± 2.4 | 11.4 ± 1.9 | > 100 | 32 ± 1.2 | 98 ± 1.3 | NT | |
11e | OCH2CH3 | 72.2 ± 5.4 | 40.1 ± 0.6 | 8.3 ± 0.2 | 75.2 ± 4.1 | 30.3 ± 2.2 | 94 ± 4.6 | NT | ||
11f [29] | OCH2CH2CH3 | 34.0 ± 3.0 | 34.4 ± 1.1 | 37.7 ± 1.1 | 45.3 ± 0.7 | 37.3 ± 1.5 | >100 | NT | ||
11g | OCH(CH3)2 | 33.3 ± 0.3 | 31.7 ± 1.7 | 36.7 ± 4.9 | 34.2 ± 0.1 | 17.1 ± 2.3 | 41.8 ± 1.5 | NT | ||
11h | OCH2CH2 CH2CH3 | 36.3 ± 2.1 | 31 ± 2.9 | 35.9 ± 1.8 | 48.2 ± 1.0 | 13.8 ± 3.5 | 65.5 ± 3.7 | NT | ||
11i | OCH2CH(CH3)2 | 42.9 ± 0.4 | 33.8 ± 0.1 | 40.1 ± 3.2 | 54.6 ± 3.6 | 30.7 ± 0.6 | 93.3 ± 3.4 | NT | ||
11j | OCHCH3CH2 OCH3 | 51.2 ± 4.1 | 32.4 ± 1.3 | 40.4 ± 2.1 | 50.0 ± 1.8 | 26.2 ± 0.5 | 76.5 ± 1.1 | NT | ||
11k | OCH2CH2OH | 64.5 ± 4.7 | 39.4 ± 1.5 | 37.8 ± 0.9 | 52.9 ± 1.6 | 38.1 ± 3.3 | 94.7 ± 2.6 | NT | ||
12a | 4-CF3-Ph | H | H | >100 | 59.1 ± 1.1 | >100 | 68.1 ± 3.3 | 43.3 ± 0.6 | >100 | >100 |
12b [22] | CH3 | >100 | 12.3 ± 0.2 | >100 | 32.8 ± 0.4 | 20.5 ± 5.1 | >100 | >100 | ||
12c | OCH3 | 81.3 ± 1.2 | 55.3 ± 1.7 | 39.3 ± 1.2 | 98 ± 2.8 | 86 ± 3.5 | 38.4 ± 3.1 | >100 | ||
13a | 2-OH-Ph | H | H | 92.7 ± 1.8 | 40.5 ± 3.1 | 25.9 ± 2.4 | 39.6 ± 3.5 | 44.7 ± 2.6 | 55.4 ± 3.6 | 81.5 ± 0.2 |
13b | CH3 | 82 ± 3.2 | 34.7 ± 0.2 | >100 | 42.8 ± 2.5 | 29.7 ± 2.3 | >100 | >100 | ||
13c | OCH3 | >100 | 54.0 ± 2.2 | 42 ± 1.8 | 73.9 ± 3.4 | 53.4 ± 2.5 | >100 | >100 | ||
14a | 4-OH-Ph | H | H | 66 ± 2.5 | 36.8 ± 0.5 | 33.9 ± 2.5 | 39.9 ± 2.6 | 42.2 ± 0.7 | 51.5 ± 1.7 | 61 ± 0.6 |
14b | CH3 | >100 | 49.3 ± 1.3 | > 100 | 93 ± 2.6 | 82.3 ± 1.8 | 54 ± 2.1 | > 100 | ||
14c | OCH3 | 82.2 ± 3.1 | 34.5 ± 0.7 | 7.3 ± 0.1 | 34.6 ± 0.3 | 52.7 ± 2.6 | 59 ± 0.2 | 76.4 ± 1.7 | ||
17a | 4-OH-Ph | H | 39.6 ± 2.1 | NT | NT | 31.4 ± 2.0 | 47.9 ± 0.2 | 28.6 ± 0.5 | NT | |
17b | CH3 | NT | >100 | NT | NT | 50.3 ± 0.6 | 22.8 ± 0.4 | NT | ||
17c | OCH3 | >100 | NT | NT | 39.8 ± 1.6 | >100 | >100 | NT | ||
18a | 3,4-diOH-Ph | H | 39.3 ± 1.9 | 29.8 ± 0.7 | NT | NT | 42.3 ± 3.3 | 11.5 ± 1.4 | NT | |
18b | CH3 | NT | 7.1 ± 0.7 | NT | 6.7 ± 0.8 | 37.4 ± 2.2 | 7.8 ± 0.3 | NT | ||
18c | OCH3 | >100 | 18.2 ± 2.9 | 8.0 ± 1.4 | >100 | >100 | >100 | >100 | ||
19a | 3-OCH3-4-OH-Ph | H | NT | 62.7 ± 2.9 | NT | 25.5 ± 1.6 | NT | 24.7 ± 2.8 | NT | |
19b | CH3 | NT | NT | NT | 34.9 ± 1.3 | 69.8 ± 1.1 | 28.9 ± 0.8 | NT | ||
19a | OCH3 | 45.3 ± 0.5 | 35.3 ± 0.6 | 34.0 ± 0.3 | 41.4 ± 2.5 | 43.1 ± 1.6 | 40.2 ± 1.2 | 66.6 ± 0.1 | ||
Cisplatin | 17.4 ± 0.2 | 15.3 ± 1.6 | 6.3 ± 0.4 | 6.5 ± 0.5 | 24.6 ± 2.1 | 25.9 ± 2.1 | 37.9 ± 1.9 |
COMP | DPPH µmol GAE/mmol | ABTS µmol GAE/mmol | FRAP µmol GAE/mmol |
11a | 20.5 (±4.0) | 150.6 (±4.7) | 62.2 (±9.9) |
11b | 18.9 (±2.3) | 5.7 (±2.7) | 47.2 (±1.0) |
11c | 23.2 (±11.9) | 41.4 (±6.7) | 27.4 (±0.9) |
11f | 227.3 (±11.0) | 175.1 (±10.4) | 183.5 (±0.9) |
13a | 14.2 (±0.4) | 292.4 (±12.4) | 125.2 (±9.4) |
13b | 7.6 (±3.8) | 116.8 (±5.8) | 41.2 (±0.7) |
13c | 30.3 (±15.4) | 214.6 (±28.4) | 43.4 (±1.8) |
14a | 12.3 (±2.3) | 194.8 (±21.4) | 105.5 (±3.4) |
14b | 7.3 (±3.1) | 84.6 (±2.7) | 114.3 (±4.2) |
14c | 21.1 (±5.8) | 75.9 (±5.3) | 42.0 (±2.0) |
17a | 16.0 (±1.1) | 227.6 (±5.4) | 161.6 (±5.7) |
17b | 20.7 (±6.6) | 218.9 (±5.6) | 156.2 (±1.1) |
17c | 13.6 (±0.9) | 209.0 (±6.6) | 134.1 (±6.7) |
18a | 520.1 (±6.9) | 401.2 (±39.2) | 480.9 (±28.8) |
18b | 589.1 (±8.9) | 487.3 (±43.9) | 564.8 (±2.2) |
18c | 551.1 (±14.9) | 298.1 (±21.0) | 432.0 (±21.4) |
19a | 223.5 (±11.2) | 564.7 (±74.5) | 307.2 (±11.9) |
19b | 225.6 (±14.7) | 410.7 (±28.9) | 262.2 (±14.2) |
19c | 207.7 (±8.6) | 456.0 (±24.6) | 296.2 (±10.4) |
p-coumaric acid | 23.0 (±3.1) | 278.8 (±11.1) | 105.2 (±4.2) |
caffeic acid | 690.7 (±36.6) | 586.0 (±32.8) | 500.0 (±33.5) |
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Kudličková, Z.; Michalková, R.; Salayová, A.; Ksiažek, M.; Vilková, M.; Bekešová, S.; Mojžiš, J. Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity. Molecules 2023, 28, 6583. https://doi.org/10.3390/molecules28186583
Kudličková Z, Michalková R, Salayová A, Ksiažek M, Vilková M, Bekešová S, Mojžiš J. Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity. Molecules. 2023; 28(18):6583. https://doi.org/10.3390/molecules28186583
Chicago/Turabian StyleKudličková, Zuzana, Radka Michalková, Aneta Salayová, Marián Ksiažek, Mária Vilková, Slávka Bekešová, and Ján Mojžiš. 2023. "Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity" Molecules 28, no. 18: 6583. https://doi.org/10.3390/molecules28186583