The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities
Abstract
:1. Introduction
2. Results and Discussion
2.1. Research of Optimal Conditions in a Model Reaction
2.2. Reactions of 5′-Halogenated-2′-Hydroxychalcones and Methoxylated Benzaldehydes
2.3. Miscellaneous Synthesized Chalcones
2.4. Green Chemistry Parameters
3. Biological Activities
3.1. Antileishmanial Activities
3.1.1. Effect of 2′-Hydroxychalcones on RAW 264.7 Cells
3.1.2. Effect of 2′-Hydrochalcones on L. donovani LV9
3.2. Antiplasmodial Activities
3.3. Antimelanoma Activities
4. Conclusions
5. Materials and Methods
5.1. Synthesis and Characterization
5.2. Biological Tests
5.2.1. Evaluation of the Antileishmanial Activity
5.2.2. Evaluation of the Antimalarial Activity on P. 3D7 Strain
5.2.3. Antimelanoma Tests against IGR-39 Cell Culture
5.3. Experimental Results in Chemistry
5.3.1. General Procedure for the 2′-Hydroxychalcone Derivatives Synthesis
5.3.2. General Procedure for the Synthesis of Compound 12 in the Conventional Method
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Entry | Base | Eq.: Ketone: Aldehyde: Base | Time Cycle × min | Additive (1 or 3 eq.) | Yields (%) |
---|---|---|---|---|---|
1 | NaOH | 1:1:1 | 2 × 15 | - | No reaction |
2 | NaOH | 1:1:2 | 2 × 15 | - | 20 |
3 | NaOH | 1:1:3 | 2 × 15 | - | 23 |
4 | LiOH | 1:1:3 | 2 × 15 | - | No reaction |
5 | KOH | 1:1:2 | 2 × 15 | - | 40 |
6 | KOH | 1:1:3 | 2 × 15 | - | 43 |
7 | KOH | 1:1:2 | 2 × 30 | - | 78 |
8 | KOH | 1:1 + 1:2 | 2 × 30 | - | 96 |
9 | KOH | 1:1:2 | 2 × 15 | K2CO3 | 54 |
10 | KOH | 1:1:2 | 1 × 60 | 1 eq. K2CO3 3 eq. K2CO3 | 74 76 |
11 | KOH | 1:2:2 | 1 × 60 | K2CO3 | 95 |
12 | KOH | 1:1:2 | 2 × 15 | 1 eq. Alumina 3 eq. Alumina | - |
1H and/or 13C | 1H Chemical Shift | 13C Chemical Shift |
---|---|---|
C=O | 192.69 | |
CH-α | 7.40 | 117.16 |
CH-β | 7.91 | 146.60 |
C-1 | 127.35 | |
CH-2 | 7.18 | 110.23 |
C-3 | 149.40 | |
C-4 | 152.10 | |
CH-5 | 6.93 | 111.2 |
CH-6 | 7.28 | 124.0 |
C-1′ | 119.62 | |
C-2′ | 159.7 | |
CH-3′ | 7.00 | 119.83 |
CH-4′ | 7.23 | 123.66 |
C-5′ | 154.85 | |
CH-6′ | 7.60 | 114.48 |
CH3-7 | 3.98 | 56.07 |
CH3-8 | 3.95 | 56.09 |
Entry | Ketone X = F, Cl, Br | Benzaldehyde | Chalcone | Yield (%) |
---|---|---|---|---|
1 | R3, R4 = OMe; R2, R5 = H | 96 | ||
2 | R2, R3 = OMe R4, R5 = H | 74 | ||
3 | R3, R4, R5 = OMe R2 = H | 84 | ||
4 | R2, R4, R5 = OMe R3 = H | 72 | ||
5 | R3, R5 = OMe R2, R4 = H | 88 | ||
6 | R3, R4 = OMe R2, R5 = H | 92 | ||
7 | R2, R3 = OMe R4, R5 = H | 95 | ||
8 | R3, R4, R5 = OMe R2 = H | 88 | ||
9 | R2, R4, R5 = OMe | -- | No reaction | |
10 | R3, R5 = OMe R2, R4 = H | 94 | ||
11 | R3, R4 = OMe R2, R5 = H | 85 | ||
12 | R2, R3 = OMe R4, R5 = H | 79 | ||
13 | R3, R4, R5 = OMe R2 = H | 86 | ||
14 | R2, R4, R5 = OMe | -- | No reaction | |
15 | R3, R5 = OMe R2, R4 = H | 94 |
Settings | In Solution | Ball Mill |
---|---|---|
Yield (%) | 47 | 86 |
Reaction time (min) | 120 | 60 |
Energy consumption (W × h) | 38 | 30 |
E-factor | 560 | 293 |
Compound | L. donovani Axenic Amastigote | L. donovani Intramacrophage Amastigote | SI * (Selectivity Index) | 3D7 P. falciparum | IGR-39 Cells Viability (24 h) | IGR-39 Cells Viability (72 h) |
---|---|---|---|---|---|---|
IC50 ± SD (µM) | IC50 ± SD (µM) | IC50 ± SD (µM) | IC50 (µM) | IC50 (µM) | ||
1 | 17.37 ± 2.64 | 5.42 ± 1.48 | 10.7 | >100 | >>100 | >>100 |
2 | 14.24 ± 2.96 | 12.80 ± 1.61 | >7.81 | 7.59 ± 1.46 | 82.7 | 54.1 |
3 | 5.59 ± 1.12 | 5.18 ± 1.68 | >19.3 | 14.12 ± 1.99 | >100 | 83.4 |
4 | 6.67 ± 1.52 | 1.59 ± 0.09 | 39 | 15.01± 0.08 | >>100 | >>100 |
5 | 8.68 ± 0.67 | ND | ND | >100 | >>100 | >>100 |
6 | 2.33 ± 0.53 | 1.36 ± 0.51 | >73.5 | 5.26 ± 0.05 | >>100 | >>100 |
7 | 4.29 ± 0.82 | 2.48 ± 0.42 | >40.3 | 8.05 ± 0.03 | >>100 | >>100 |
8 | 9.82 ± 2.47 | 9.82 ± 2.47 | >10.2 | 10.21 ± 2.56 | >100 | 70.5 |
9 | 8.59 ± 1.08 | ND | ND | 13.41 ± 1.54 | >>100 | >>100 |
10 | 5.87 ± 2.11 | 10.03 ± 2.14 | >9.97 | 36.84 ± 2.54 | >>100 | >>100 |
11 | 2.82 ± 0.77 | 3.29 ± 1.99 | >30.4 | 51.35 ± 2.54 | >>100 | >>100 |
12 | >100 | >100 | ND | 17.51 ± 2.18 | 91 | 24.7 |
13 | 11.52 ± 0.47 | 15.22 ± 1.43 | >6.57 | 15.11 ± 1.29 | >100 | 51.5 |
14 | 11.38 ± 2.52 | 22.91 ± 3.91 | >4.36 | >100 | >>100 | >>100 |
15 | 9.44 ± 2.20 | 2.87 ± 0.36 | >34.8 | 3.21 | >>100 | >>100 |
16 | 11.23 ± 2.06 | 13.49 ± 2.99 | >7.41 | 53.43 ± 4.16 | >>100 | >>100 |
17 | 24.24 ± 2.56 | 18.41 ± 2.33 | 2.62 | 6.13 ± 0.51 | 66.3 | 38.6 |
Reference | 3.66 ± 0.73 a | 5.78 ± 1.02 a | 9 a | 0.012 ± 0.002 b | 372.0 c | 25.0 c |
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Abid, I.; Moslah, W.; Cojean, S.; Imbert, N.; Loiseau, P.M.; Chamayou, A.; Srairi-Abid, N.; Calvet, R.; Baltas, M. The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities. Molecules 2024, 29, 1819. https://doi.org/10.3390/molecules29081819
Abid I, Moslah W, Cojean S, Imbert N, Loiseau PM, Chamayou A, Srairi-Abid N, Calvet R, Baltas M. The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities. Molecules. 2024; 29(8):1819. https://doi.org/10.3390/molecules29081819
Chicago/Turabian StyleAbid, Imen, Wassim Moslah, Sandrine Cojean, Nicolas Imbert, Philippe M. Loiseau, Alain Chamayou, Najet Srairi-Abid, Rachel Calvet, and Michel Baltas. 2024. "The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities" Molecules 29, no. 8: 1819. https://doi.org/10.3390/molecules29081819
APA StyleAbid, I., Moslah, W., Cojean, S., Imbert, N., Loiseau, P. M., Chamayou, A., Srairi-Abid, N., Calvet, R., & Baltas, M. (2024). The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities. Molecules, 29(8), 1819. https://doi.org/10.3390/molecules29081819