Novel Thiazolo[5,4-b]phenothiazine Derivatives: Synthesis, Structural Characterization, and In Vitro Evaluation of Antiproliferative Activity against Human Leukaemia
Abstract
:1. Introduction
2. Results
2.1. Synthesis of Thiazolo[5,4-b]phenothiazine Derivatives
2.2. Spectral Properties
2.3. Computational Data
2.4. Biological Properties
3. Discussion
4. Materials and Methods
4.1. General Procedure for Obtaining N-Acyl-3-Aminophenothiazines (1a–e)
4.2. General Procedure for Obtaining N-(Phenothiazin-3-yl)tioamides (2a–e)
4.3. General Procedure for Obtaining Thiazolo[5,4-b]phenothiazine (3a–e)
4.4. Biologic Assay
4.4.1. Cell Cultures
4.4.2. Cell Viability Tests
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Cpd | λmax,abs 1 (nm) (ε (M−1 cm−1)) | λmax, em 2 (nm) | Stokes Shift 3 (cm−1) | Egap,opt 4 (eV) | EHOMO 5 (eV) | ELUMO 5 (eV) | Dipole Moment 5 (D) |
---|---|---|---|---|---|---|---|
3a | 263 (28,900) 326 (7400) | 447 | 8300 | 4.49 | −5.07 | −0.78 | 2.68 |
3b | 261 (43,400) 370 (15,800) | 550 | 8800 | 4.28 | −5.07 | −1.54 | 2.67 |
3c | 262 (32,800) 377 (12,200) | 564 | 8800 | 4.18 | −5.17 | −1.77 | 3.92 |
3d | 264 (29,600) 300 (12,600) 424 (9300) | - | - | −5.36 | −2.72 | 7.63 | |
3e | 250 (23,300) 294 (8900) 373 (8900) | 608 | 10,400 | 4.07 | −5.07 | −1.69 | 2.55 |
Cpd | Antiproliferative Activity IC50 (μM) | ||
---|---|---|---|
THP-1 | HL-60 | PBMC | |
2a | 101.70 ± 0.11 b | 175.8 ± 0.23 b | >2000 |
2b | 1481 a | >2000 | 1121 |
2c | 88.9 ± 0.03 b | 69.1 ± 0.19 b | >2000 |
2e | >2000 | >2000 | 227 a |
3a | 463.4 ± 0.16 b | 194.3 ± 0.17 b | >2000 |
3b | 1241 a | 338.9 ± 0.14 b | 1906 a |
3c | >1000 | 1066 a | >1000 |
3e | 21.6 ± 0.06 b | 67.2 ± 0.09 b | >2000 |
Cytarabine | 9.0 ± 0.05 b | 13.5 ± 0.05 b |
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Brem, B.; Gal, E.; Găină, L.; Silaghi-Dumitrescu, L.; Fischer-Fodor, E.; Tomuleasa, C.I.; Grozav, A.; Zaharia, V.; Filip, L.; Cristea, C. Novel Thiazolo[5,4-b]phenothiazine Derivatives: Synthesis, Structural Characterization, and In Vitro Evaluation of Antiproliferative Activity against Human Leukaemia. Int. J. Mol. Sci. 2017, 18, 1365. https://doi.org/10.3390/ijms18071365
Brem B, Gal E, Găină L, Silaghi-Dumitrescu L, Fischer-Fodor E, Tomuleasa CI, Grozav A, Zaharia V, Filip L, Cristea C. Novel Thiazolo[5,4-b]phenothiazine Derivatives: Synthesis, Structural Characterization, and In Vitro Evaluation of Antiproliferative Activity against Human Leukaemia. International Journal of Molecular Sciences. 2017; 18(7):1365. https://doi.org/10.3390/ijms18071365
Chicago/Turabian StyleBrem, Balazs, Emese Gal, Luiza Găină, Luminiţa Silaghi-Dumitrescu, Eva Fischer-Fodor, Ciprian Ionuţ Tomuleasa, Adriana Grozav, Valentin Zaharia, Lorena Filip, and Castelia Cristea. 2017. "Novel Thiazolo[5,4-b]phenothiazine Derivatives: Synthesis, Structural Characterization, and In Vitro Evaluation of Antiproliferative Activity against Human Leukaemia" International Journal of Molecular Sciences 18, no. 7: 1365. https://doi.org/10.3390/ijms18071365