Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Cytotoxic Activity
2.3. Apoptotic Activity
2.3.1. Cell Morphology
2.3.2. Cell Cycle Analysis
2.3.3. Mitochondrial Membrane Potential (ΔΨm) Analysis
2.3.4. Translocation of Phosphatidylserine to Outer Leaflet of Cell Membrane
3. Materials and Methods
3.1. Synthesis
3.2. Crystallographic Details
3.3. Cell Culture and Cell Viability Assay
3.3.1. Cell Morphology
3.3.2. Mitochondrial Membrane Potential (Δψm) Analysis
3.3.3. Translocation of Phosphatidylserine to the Outer Leaflet of Cell Membrane
3.3.4. Statistical Analysis
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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Compd | R1 | R2 | IC50 [μM] | |||
---|---|---|---|---|---|---|
MCF-7 | HeLa | HCT-116 | HaCaT | |||
8 | H | H | 130 ± 8 | 120 ± 8 | 167 ± 7 | - |
9 | H | 2-OH | 18 ± 1 | 17 ± 1 | 11 ± 0.5 | 35 ± 1 |
10 | H | 4-OH | 15 ± 1 | 15 ± 1 | 9 ± 0.1 | 31 ± 1 |
11 | H | 4-OMe | 330 ± 17 | nd | 300 ± 21 | - |
12 | H | 4-Cl | 210 ± 13 | 190 ± 10 | 113 ± 6 | - |
13 | H | 4-NO2 | 370 ± 20 | 340 ± 31 | 320 ± 10 | - |
14 | 2-MeC6H4 | 2-OH | 13 ± 0.6 | 18 ± 1 | 9 ± 0.1 | 31 ± 2 |
15 | 2-MeC6H4 | 4-OH | 13 ± 0.4 | 18 ± 0.5 | 10 ± 0.6 | 33 ± 2 |
16 | 3-MeC6H4 | 2-OH | 20 ± 0.5 | 36 ± 2 | 17 ± 0.1 | 41 ± 2 |
17 | 3-MeC6H4 | 4-OH | 17 ± 1 | 21 ± 1 | 12 ± 0.6 | 35 ± 2 |
18 | 4-MeC6H4 | H | 260 ± 15 | 200 ± 10 | 160 ± 5 | - |
19 | 4-MeC6H4 | 2-OH | 14 ± 1 | 23 ± 1 | 11 ± 0.2 | 36 ± 2 |
20 | 4-MeC6H4 | 4-OH | 15 ± 1 | 15 ± 1 | 8.5 ± 0.2 | 31 ± 1 |
21 | 4-MeC6H4 | 4-OMe | 150 ± 10 | 250 ± 12 | 235 ± 5 | - |
22 | 4-MeC6H4 | 4-Cl | 193 ± 10 | 705 ± 35 | 183 ± 13 | - |
23 | 4-MeC6H4 | 4-NO2 | 280 ± 17 | 170 ± 10 | nd | - |
24 | 2-ClC6H4 | 2-OH | 12 ± 0.6 | 17 ± 0.5 | 9 ± 0.5 | 33 ± 2 |
25 | 2-ClC6H4 | 4-OH | 19 ± 1 | 18 ± 0.5 | 15 ± 0.6 | 41 ± 2 |
26 | 3-ClC6H4 | 2-OH | 13 ± 0.6 | 19 ± 0.5 | 10 ± 0.4 | 38 ± 2 |
27 | 3-ClC6H4 | 4-OH | 16 ± 1 | 20 ± 0.5 | 12 ± 0.1 | 37 ± 2 |
28 | 4-ClC6H4 | H | 230 ± 12 | 20 ± 1 | 220 ± 11 | 99 ± 3 |
29 | 4-ClC6H4 | 2-OH | 19 ± 1 | 41 ± 2 | 18 ± 0.4 | 45 ± 3 |
30 | 4-ClC6H4 | 4-OH | 18 ± 1 | 37 ± 1 | 8 ± 0.2 | 85 ± 2 |
31 | 4-ClC6H4 | 4-OMe | 230 ± 13 | 110 ± 5 | 365 ± 11 | - |
32 | 4-ClC6H4 | 4-Cl | 198 ± 10 | nd | 204 ± 12 | - |
33 | 4-ClC6H4 | 4-NO2 | 220 ± 12 | 110 ± 3 | 450 ± 27 | - |
Cisplatin | 3.0 ± 0.1 | 2.2 ± 0.1 | 3.8 ± 0.2 | 7.7 ± 0.2 |
Compd | R1 | R2 | Selectivity Index | ||
---|---|---|---|---|---|
MCF-7/HaCaT | HeLa/HaCaT | HCT-116/HaCaT | |||
9 | H | 2-OH | 1.9 | 2.1 | 3.2 |
10 | H | 4-OH | 2.1 | 2.1 | 3.4 |
14 | 2-MeC6H4 | 2-OH | 2.4 | 1.7 | 3.4 |
15 | 2-MeC6H4 | 4-OH | 2.5 | 1.8 | 3.3 |
16 | 3-MeC6H4 | 2-OH | 2.0 | ns | 2.4 |
17 | 3-MeC6H4 | 4-OH | 2.1 | 1.7 | 2.9 |
19 | 4-MeC6H4 | 2-OH | 1.9 | 1.6 | 3.3 |
20 | 4-MeC6H4 | 4-OH | 2.1 | 2.1 | 3.6 |
24 | 2-ClC6H4 | 2-OH | 2.7 | 1.9 | 3.7 |
25 | 2-ClC6H4 | 4-OH | 2.2 | 2.3 | 2.7 |
26 | 3-ClC6H4 | 2-OH | 2.9 | 2.0 | 3.8 |
27 | 3-ClC6H4 | 4-OH | 2.3 | 1.8 | 3.1 |
29 | 4-ClC6H4 | 2-OH | 2.4 | ns | 2.5 |
30 | 4-ClC6H4 | 4-OH | 4.7 | 2.3 | 10.6 |
Cisplatin | 2.6 | 3.5 | 2.0 |
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Pogorzelska, A.; Sławiński, J.; Kawiak, A.; Stasiłojć, G.; Chojnacki, J. Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells. Int. J. Mol. Sci. 2023, 24, 4436. https://doi.org/10.3390/ijms24054436
Pogorzelska A, Sławiński J, Kawiak A, Stasiłojć G, Chojnacki J. Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells. International Journal of Molecular Sciences. 2023; 24(5):4436. https://doi.org/10.3390/ijms24054436
Chicago/Turabian StylePogorzelska, Aneta, Jarosław Sławiński, Anna Kawiak, Grzegorz Stasiłojć, and Jarosław Chojnacki. 2023. "Synthesis of 3-(2-Alkylthio-4-chloro-5-methylbenzenesulfonyl)-2-(1-phenyl-3-arylprop-2-enylideneamino)guanidine Derivatives with Pro-Apoptotic Activity against Cancer Cells" International Journal of Molecular Sciences 24, no. 5: 4436. https://doi.org/10.3390/ijms24054436