Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Lipophilicity
No. | Structure | R1 | R2 | log P | log k | MIC M. tuberculosis [µg/mL] | IC50 [mmol/L] | |
---|---|---|---|---|---|---|---|---|
Group A | 1 | CH3 | - | −0.17 | −0.747 | >100 | ND | |
2 | C2H5 | - | 0.16 | −0.591 | >100 | ND | ||
3 | C3H7 | - | 0.65 | −0.414 | >100 | ND | ||
4 | C4H9 | - | 1.07 | −0.209 | >100 | 4.014 | ||
5 | C5H11 | - | 1.49 | 0.012 | >100 | 1.390 | ||
6 | C6H13 | - | 1.90 | 0.239 | 100 | 1.067 | ||
7 | C7H15 | - | 2.32 | 0.470 | 100 | 0.256 | ||
8 | C8H17 | - | 2.74 | 0.702 | 50 | 0.055 | ||
Group B | 9 | CH3 | CH3 | −0.86 | −0.279 | >100 | 5.646 | |
10 | C2H5 | −0.52 | −0.052 | >100 | ND | |||
11 | C3H7 | −0.04 | 0.166 | >100 | ND | |||
12 | C4H9 | 0.38 | 0.401 | 100 | 0.523 | |||
13 | C5H11 | 0.80 | 0.638 | 50 | 0.544 | |||
14 | C6H13 | 1.21 | 0.876 | 25 | 0.125 | |||
15 | C7H15 | 1.63 | 1.118 | 25 | 0.065 | |||
16 | C8H17 | 2.05 | 1.359 | 25 | 0.064 | |||
Group C | 17 | C2H5 | CH3 | −0.52 | −0.063 | >100 | ND | |
18 | C2H5 | −0.19 | 0.163 | >100 | ND | |||
19 | C3H7 | 0.30 | 0.382 | >100 | 2.047 | |||
20 | C4H9 | 0.72 | 0.617 | >100 | 1.090 | |||
21 | C5H11 | 1.13 | 0.855 | 50 | 0.301 | |||
22 | C6H13 | 1.55 | 1.094 | 50 | 0.078 | |||
23 | C7H15 | 1.97 | 1.337 | 50 | 0.048 | |||
24 | C8H17 | 2.39 | 1.579 | 50 | 0.056 | |||
Group D | 25 | C3H7 | C3H7 | 0.79 | 0.600 | >100 | 1.303 | |
26 | C4H9 | C4H9 | 1.62 | 1.077 | 50 | 0.202 | ||
27 | C5H11 | C5H11 | 2.46 | 1.557 | >100 | 0.105 | ||
28 | C6H13 | C6H13 | 3.29 | 2.041 | >100 | 0.272 | ||
29 | C7H15 | C7H15 | 4.12 | 2.503 | >100 | 1.123 | ||
30 | C8H17 | C8H17 | 4.96 | 2.981 | >100 | 0.752 | ||
DCMU | 2.2 | 0.002 | ||||||
INH | −0.64 | 0.1−0.39 |
2.3. Biological Activity
2.3.1. Antimycobacterial Activity
2.3.2. Antibacterial and Antifungal Activity
Compound No. | MIC [µmol/L] |
---|---|
6 | 250 |
7 | 125 |
8 | 62.5 |
13 | 250 |
14 | 250 |
15 | 125 |
21 | 250 |
22 | 125 |
23 | 125 |
2.3.4. Cytotoxicity Assay
2.3.5. Evaluation of Photosynthetic Electron Transport (PET) Inhibiting Activity
3. Experimental Section
3.1. General Information
3.2. Synthesis
3.3. Analytical Data
3.4. Determination of Lipophilicity by HPLC (Log k)
3.5. Biological Assays
3.5.1. Evaluation of in Vitro Antimycobacterial Activity
3.5.2. Evaluation of in Vitro Antibacterial Activity
3.5.3. Evaluation of in Vitro Antifungal Activity
3.5.5. Study of Inhibition of Photosynthetic Electron Transport (PET) in Spinach Chloroplasts
3.5.6. Study of Fluorescence of Aromatic Amino Acids in Spinach Chloroplasts
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Semelkova, L.; Konecna, K.; Paterova, P.; Kubicek, V.; Kunes, J.; Novakova, L.; Marek, J.; Naesens, L.; Pesko, M.; Kralova, K.; et al. Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides. Molecules 2015, 20, 8687-8711. https://doi.org/10.3390/molecules20058687
Semelkova L, Konecna K, Paterova P, Kubicek V, Kunes J, Novakova L, Marek J, Naesens L, Pesko M, Kralova K, et al. Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides. Molecules. 2015; 20(5):8687-8711. https://doi.org/10.3390/molecules20058687
Chicago/Turabian StyleSemelkova, Lucia, Klara Konecna, Pavla Paterova, Vladimir Kubicek, Jiri Kunes, Lucie Novakova, Jan Marek, Lieve Naesens, Matus Pesko, Katarina Kralova, and et al. 2015. "Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides" Molecules 20, no. 5: 8687-8711. https://doi.org/10.3390/molecules20058687