Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity
Abstract
:1. Introduction
2. Results and Discussion
3. Methods
3.1. Chemistry
3.1.1. 10-(4-Pyrrolidin-1-yl-but-2-ynyl)-1,6-diazaphenothiazine (1)
3.1.2. 10-(4-Piperidin-1-yl-but-2-ynyl)- 1,6-diazaphenothiazine (2)
3.1.3. 10-(4-Morpholin-4-yl-but-2-ynyl)-1,6-diazaphenothiazine (3)
3.2. Molecular Modeling
3.3. Biological Tests
3.3.1. AChE/BuChE-Inhibitory Activity
3.3.2. Kinetic Studies
4. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | R | % Inhibition +/− Ϭ a | IC50 eeAChE b [µM] +/− SEM c | % Inhibition +/− Ϭ | IC50 eqBuChE d [µM] +/− SEM | |
---|---|---|---|---|---|---|
Dipyridothiazines | ||||||
isomer 1,6-diaza | 1 | 45.4 ± 9.8 | — | 65.4 ± 3.0 | 5.748 ± 0.164 | |
2 | 60.3 ± 8.8 | 8.309 ± 0.315 | 56.6 ± 2.4 | 8.942 ± 0.239 | ||
3 | 13.7 ± 1.5 | — | 63.6 ± 2.4 | 9.250 ± 0.275 | ||
4 | 22.4 ± 1.1 | — | 57.0 ± 7.4 | 9.493 ± 0.330 | ||
5 | 7.3 ± 0.9 | — | 52.5 ± 5.9 | 10.080 ± 0.441 | ||
isomer 1,8-diaza | 6 | (CH2)3N(CH3)2 | 20.4 ± 3.6 | — | 85.8 ± 0.5 | 0.865 ± 0.011 |
7 | 57.3 ± 0.4 | 10.020 ± 0.604 | 91.1 ± 0.8 | 0.929 ± 0.016 | ||
8 | 33.5 ± 1.6 | — | 66.0 ± 3.4 | 4.442 ± 0.049 | ||
9 | 58.1 ± 4.1 | 6.546 ± 0.177 | 76.4 ± 0.2 | 3.034 ± 0.072 | ||
10 | 49.6 ± 1.3 | 9.410 ± 0.489 | 71.9 ± 4.3 | 3.666 ± 0.054 | ||
isomer 2,7-diaza | 11 | 20.1 ± 1.4 | — | 20.7 ± 0.9 | — | |
12 | 20.3 ± 1.0 | — | 31.4 ± 1.7 | — | ||
13 | 51.6 ± 3.2 | 11.330 ± 0.464 | 37.6 ± 1.6 | — | ||
isomer 3,6-diaza | 14 | 7.7 ± 2.1 | — | 20.4 ± 1.9 | — | |
15 | 10.1 ± 3.1 | — | 17.2 ± 7.3 | — | ||
16 | 21.9 ± 5.7 | — | 58.5 ± 9.0 | 10.380 ± 0.308 | ||
17 | 33.0 ± 4.5 | — | 16.1 ± 0.7 | — | ||
18 | 72.2 ± 0.7 | 4.263 ± 0.078 | 30.5 ± 5.7 | — | ||
N-substituted 9-fluoroquinobenzothiazines | ||||||
19 | H | 6.6 ± 1.3 | — | 81.0 ± 1.4 | 1.020 ± 0.028 | |
20 | CH3 | 3.0 ± 1.6 | — | 35.3 ± 12.3 | — | |
21 | (CH2)3NH2 | 6.5 ± 2.8 | — | 76.3 ± 1.2 | 2.511 ± 0.047 | |
22 | (CH2)4NH2 | 2.3 ± 2.1 | — | 64.7 ± 1.0 | 3.929 ± 0.196 | |
23 | 27.0 ± 2.8 | — | 97.7 ± 0.5 | 0.463 ± 0.010 | ||
N-substituted 9-methylthioquinobenzothiazines | ||||||
24 | 83.4 ± 1.1 | 0.784 ± 0.018 | 95.5 ± 0.8 | 0.535 ± 0.013 | ||
25 | 78.0 ± 1.4 | 2.218 ± 0.062 | 99.9 ± 0.7 | 0.506 ± 0.014 | ||
Reference | ||||||
Tacrine | 0.024 ± 0.001 | 0.002 ± 0.0005 |
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Jończyk, J.; Godyń, J.; Stawarska, E.; Morak-Młodawska, B.; Jeleń, M.; Pluta, K.; Malawska, B. Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity. Molecules 2020, 25, 2604. https://doi.org/10.3390/molecules25112604
Jończyk J, Godyń J, Stawarska E, Morak-Młodawska B, Jeleń M, Pluta K, Malawska B. Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity. Molecules. 2020; 25(11):2604. https://doi.org/10.3390/molecules25112604
Chicago/Turabian StyleJończyk, Jakub, Justyna Godyń, Ewelina Stawarska, Beata Morak-Młodawska, Małgorzata Jeleń, Krystian Pluta, and Barbara Malawska. 2020. "Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity" Molecules 25, no. 11: 2604. https://doi.org/10.3390/molecules25112604