Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Synthesis
2.1.1. Cinnamylation of DHC 1
2.1.2. Benzylation of DHC 1
2.1.3. Prenylation of DHC 1
2.2. Biological Evaluation of Alkylated DHCs 3a–e, 5a–d, 7a–b, and 8a
3. Materials and Methods
3.1. General Information
3.1.1. Chemistry
3.1.2. Antibacterial Assays
3.1.3. Cytotoxicity Assays
3.2. Synthesis of Compounds 3a–e
3.2.1. General Procedure for the Cinnamylation of DHC 1
3.2.2. Compound 3a
3.2.3. Compound 3b
3.2.4. Compound 3c
3.2.5. Compound 3d
3.2.6. Compound 3e
3.2.7. Compound 3e’
3.3. Synthesis of Compounds 5a–d
3.3.1. General Procedure for the Benzylation of DHC 1
3.3.2. Compound 5a
3.3.3. Compound 5b
3.3.4. Compound 5c
3.3.5. Compound 5d
3.4. Synthesis of Compounds 7a–b and 8a–b
3.4.1. Prenylation of DHC 1
3.4.2. Compound 7a
3.4.3. Compound 7b
3.4.4. Geranylation of DHC 1
3.4.5. Compound 8a
3.4.6. Compound 8b
4. Conclusions
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 | Alcohol 2 (R 1, R 2) | Product 3 (Yield) 1 |
1 | 2a (OH, H) | 3a (69%) |
2 | 2b (OCH3, H) | 3b (49%) |
3 | 2c (OCH3, OCH3) | 3c (61%) |
4 2 | 2d (H, H) | 3d (72%) |
5 2 | 2e (Cl, H) | 3e (30%) |
| ||
---|---|---|
Entry | Alcohol 4 (R 1, R 2) | Product 5 (Yield) 1 |
1 | 4a (OH, H) | 5a (61%) |
2 | 4b (H, OH) | 5b (74%) |
3 2 | 4c (H, OCH3) | 5c (36%) |
4 | 4d (H, Cl) | 5d (36%) |
| ||
---|---|---|
Entry | Alcohol 6 (Equiv) | Product Ratio 7a:7b 1 (Yield) 2 |
1 | 6a (0.25 equiv) | 1:1 (40%) |
2 | 6a (0.50 equiv) | 1.3:1 (48%) |
3 | 6a (1.0 equiv) | 2.1:1 (46%) |
4 | 6b (0.25 equiv) | 1.4:1 (58%) |
5 | 6b (0.50 equiv) | 1.4:1 (44%) |
6 | 6b (1.0 equiv) | 1.9:1 (26%) |
Entry | Product | MIC90 (µM) 1 | IC50 (µM) 1,6 | |||
---|---|---|---|---|---|---|
E. coli | S. aureus | A-549 | DLD-1 | WS-1 | ||
1 | 3a | >100 | 11.6 ± 0.2 | 36 ± 3 | 28 ± 5 | 57 ± 4 |
2 | 3b | >100 | 5.7 ± 0.1 | 47 ± 6 | 26 ± 8 | 56 ± 5 |
3 | 3c | >100 | 6.0 ± 0.1 | 30 ± 3 | 36 ± 4 | 57 ± 6 |
4 | 3d | >100 | 5 ± 0.9 | 43 ± 4 | 35 ± 6 | 58 ± 3 |
5 | 3e | >100 | 2.6 ± 0.4 | 44 ± 3 | 44 ± 7 | 59 ± 5 |
6 | 5a | >100 | 12 ± 1 | >100 | >100 | >100 |
7 | 5b | >100 | 20 ± 1 | 52 ± 9 | 64 ± 5 | 60 ± 5 |
8 | 5c | >100 | 4.2 ± 0.5 | 25 ± 2 | 29 ± 3 | 39 ± 4 |
9 | 5d | >100 | 2.3 ± 0.1 | 38 ± 2 | 46 ± 3 | 44 ± 4 |
10 | 7a | >100 | 80 ± 3 | >100 | >100 | >100 |
11 | 7b | >100 | 98 ± 1 | >100 | >100 | >100 |
12 | 8a | >100 | 2.5 ± 0.3 | 28 ± 2 | 21 ± 3 | 35 ± 4 |
13 | Balsacone A 2 | >100 | 3.3 ± 0.2 | 44 ± 4 | 31 ± 5 | 56 ± 4 |
14 | Gentamicin 2 | 0.083 ± 0.007 3 | 0.12 ± 0.01 3 | n. d. 4 | n. d. | n. d. |
15 | Etoposide 5 | n. d. | n. d. | 0.56 ± 0.04 | 0.96 ± 0.08 | 10 ± 5 |
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Ardaillou, A.; Alsarraf, J.; Legault, J.; Simard, F.; Pichette, A. Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor. Antibiotics 2021, 10, 620. https://doi.org/10.3390/antibiotics10060620
Ardaillou A, Alsarraf J, Legault J, Simard F, Pichette A. Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor. Antibiotics. 2021; 10(6):620. https://doi.org/10.3390/antibiotics10060620
Chicago/Turabian StyleArdaillou, Anne, Jérôme Alsarraf, Jean Legault, François Simard, and André Pichette. 2021. "Hemisynthesis and Biological Evaluation of Cinnamylated, Benzylated, and Prenylated Dihydrochalcones from a Common Bio-Sourced Precursor" Antibiotics 10, no. 6: 620. https://doi.org/10.3390/antibiotics10060620