New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Antimalarial Evaluation
2.3. Structure Activity Relationship
3. Experimental Section
3.1. General Information
3.2. Synthesis
3.2.1. General Procedure for the Synthesis of Dihydropyrimidines (DHPMs) 4a–j
3.2.2. General Procedure for the Synthesis of Chalcones 6a,b
3.2.3. General Procedure for the Synthesis of 7a,b
3.3. Anti-Plasmodial Assay
3.4. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Compound | R1 | R2 | X | Yield % | Compound | R1 | R2 | X | Yield % |
---|---|---|---|---|---|---|---|---|---|
4a | OEt | O | 89 | 4f | OEt | S | 88 | ||
4b | OEt | S | 86 | 4g | Me | S | 86 | ||
4c | Me | O | 87 | 4h | Me | O | 85 | ||
4d | Me | S | 85 | 4i | Me | S | 89 | ||
4e | OEt | O | 88 | 4j | OEt | S | 85 |
Compound | % Mean Parasite Inhibition Per 1500 RBC | |||||||
---|---|---|---|---|---|---|---|---|
Concentrations (μg/mL) | ||||||||
0.625 | 1.25 | 2.5 | 5 | |||||
Range | Mean ± SE | Range | Mean ± SE | Range | Mean ± SE | Range | Mean ± SE | |
4a | 2.0–7.8 | 5.7 ± 1.85 | 8.2–18.2 | 14.1 ± 3.02 | 31.3–41.8 | 36.6 ± 3.03 | 47.1–53.1 | 51.0 ± 1.93 |
4c | 14.2–15.6 | 14.7 ± 0.42 | 26.5–36.3 | 35.3 ± 3.09 | 54.5–62.7 | 57.4 ± 2.63 | 85.7–92.1 | 89.5 ± 1.96 |
4d | 2.0–5.4 | 3.7 ± 0.98 | 0.0–3.6 | 1.8 ± 1.03 | 6.1–7.8 | 7.1 ± 0.49 | 14.3–18.1 | 16.1 ± 1.11 |
4e | 0.0–2.0 | 1.3 ± 0.63 | 2.0–7.2 | 4.4 ± 1.51 | 13.7–14.2 | 14.1 ± 0.23 | 24.4–35.2 | 29.5 ± 3.12 |
4f | 9.8–12.2 | 10.9 ± 0.69 | 27.4–29.1 | 28.3 ± 0.49 | 32.7–43.1 | 37.5 ± 3.02 | 69.1–78.4 | 72.9 ± 2.79 |
4h | 20.4–23.6 | 21.8 ± 0.93 | 24.5–35.2 | 31.4 ± 3.05 | 69.1–75.5 | 72.3 ± 1.84 | 80–83.7 | 82.0 ± 1.07 |
4j | 1.9–7.2 | 3.7 ± 1.75 | 0.0–5.4 | 2.5 ± 1.57 | 19.6–20.4 | 20.0 ± 0.23 | 49–56.8 | 51.6 ± 2.58 |
6b | 42.8–43.6 | 43.2 ± 0.23 | 52.7–62.7 | 56.2 ± 3.26 | 55.1–69.1 | 61.0 ± 4.18 | 100–100 | 100 ± 00 |
7a | 27.4–29.1 | 29.1 ± 0.92 | 37.3–45.5 | 42.6 ± 2.63 | 64.7–67.3 | 66.4 ± 0.86 | 66.7–73.5 | 71.0 ± 2.14 |
7b | 34.5–35.3 | 34.8 ± 0.25 | 54.5–55.1 | 54.8 ± 0.17 | 78.4–89.1 | 83.0 ± 3.17 | 100–100 | 100 ± 00 |
8 | 35.3–50.1 | 42.3 ± 4.3 | 63.3–76.4 | 70.1 ± 3.8 | 100–100 | 100 ± 00 | - | - |
10 | 11.8–25.5 | 17.2 ± 4.21 | 43.1–60 | 51.4 ± 4.88 | 67.3–74.5 | 70.3 ± 2.16 | 84.3–84.3 | 84.3 ± 00 |
11 | 5.9–18.2 | 12.8 ± 3.62 | 39.2–49 | 44.6 ± 2.86 | 63.2–74.5 | 70.1 ± 350 | 75.5–83.6 | 80.0 ± 2.51 |
12 | 35.3–45.4 | 41.8 ± 3.27 | 59.2–70.9 | 64.3 ± 3.46 | 74.5–78.2 | 76.7 ± 1.13 | 86.3–91.8 | 89.7 ± 1.70 |
CQ | 59.9–63.8 | 61.8 ± 1.13 | 75.9–78.1 | 76.7 ± 0.67 | 100–100 | 100 ± 0.0 | - | - |
Concentrations (μg/mL) | Compound | ||||
---|---|---|---|---|---|
4b | 4g | 4i | CQ | ||
0.078 | Range | NP | NP | 32.7–36.7 | NP |
Mean ± SE | NP | NP | 34.8 ± 1.16 | NP | |
0.156 | Range | NP | 23.5–25.4 | NP | 28.9–33.7 |
Mean ± SE | NP | 24.4 ± 0.54 | NP | 31.8 ± 1.44 | |
0.312 | Range | 41.8–44.9 | 56.3–61.2 | 63.6–71.4 | 43.3–46.4 |
Mean ± SE | 43.3 ± 0.89 | 58.7 ± 1.41 | 67.8 ± 2.28 | 44.9 ± 0.90 | |
0.625 | Range | 55.1–70.1 | 82.3–89.7 | 74.5–86.2 | 59.9–63.8 |
Mean ± SE | 63.3 ± 4.38 | 87.0 ± 2.35 | 79.4 ± 3.5 | 61.8 ± 1.13 | |
1.25 | Range | 73.5–82.3 | 100–100 | 85.7–94.1 | 75.9–78.1 |
Mean ± SE | 76.7 ± 2.78 | 100 ± 0.0 | 89.9 ± 2.59 | 76.7 ± 0.67 | |
2.5 | Range | 89.1–95.9 | - | 100–100 | 100–100 |
Mean ± SE | 91.7 ± 2.11 | - | 100 ± 0.0 | 100 ± 0.0 | |
5 | Range | 100–100 | - | - | - |
Mean ± SE | 100 ± 0.0 | - | - | - |
Compound | IC50 (μg/mL) | Slope | R2 |
---|---|---|---|
4a | 4.59 | 10.32 | 0.929 |
4b | 0.46 | 10.43 | 0.772 |
4c | 2.39 | 16.28 | 0.968 |
4d | 15.87 | 3.17 | 0.932 |
4e | 8.10 | 6.55 | 0.997 |
4f | 3.29 | 13.34 | 0.977 |
4g | 0.30 | 61.62 | 0.791 |
4h | 2.21 | 14.0 | 0.831 |
4i | 0.014 | 23.48 | 0.733 |
4j | 4.96 | 11.67 | 0.975 |
6a | 1.13 | 12.41 | 0.965 |
7a | 2.09 | 9.11 | 0.790 |
7b | 1.06 | 14.14 | 0.889 |
8 | 0.76 | 29.79 | 0.971 |
10 | 1.91 | 13.27 | 0.782 |
11 | 2.21 | 13.59 | 0.767 |
12 | 0.46 | 9.62 | 0.834 |
CQ | 0.49 | 27.01 | 0.927 |
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Radini, I.A.M.; Elsheikh, T.M.Y.; El-Telbani, E.M.; Khidre, R.E. New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents. Molecules 2016, 21, 909. https://doi.org/10.3390/molecules21070909
Radini IAM, Elsheikh TMY, El-Telbani EM, Khidre RE. New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents. Molecules. 2016; 21(7):909. https://doi.org/10.3390/molecules21070909
Chicago/Turabian StyleRadini, Ibrahim Ali M., Tarek M. Y. Elsheikh, Emad M. El-Telbani, and Rizk E. Khidre. 2016. "New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents" Molecules 21, no. 7: 909. https://doi.org/10.3390/molecules21070909