Recent Advances in the Studies on Luotonins
Abstract
:1. Introduction
Compound | Luotonin A | Luotonin B | Luotonin C | Luotonin D | Luotonin E | Luotonin F |
---|---|---|---|---|---|---|
IC50 (μg/mL) | 1.8 | 5.0 | - | - | 9.0 | 2.3 |
2. Synthesis
2.1. via Formation of the Pyridine Core
2.2. via Formation of the Pyrrole Core
2.3. via Formation of the Pyrimidinone Core
2.4. via Formation of the Pyrrolo[4,3-b]pyridine Core
2.5. via Formation of the Pyrrolo[1,2-a]pyrimidin-4(6H)-one Core
2.6. Formation of Rings B, C and D
2.7. Conversion of Luotonin A to Luotonins B and E
3. Synthesis of Luotonin C and D
4. Synthesis of Luotonin E and F
5. Structural Modifications and Structure-Activity Relationships
5.1. Modifications on Ring A
5.2. Modifications on Ring C
Compd | R1 | R2 | R3 | R14 | Inhibitory activity against Topo I [% (rel. activity)] at 100 μM | IC50 (μM) | ||
---|---|---|---|---|---|---|---|---|
HCT-116 | HL-60 | H460 | ||||||
1aa | H | H | H | H | 33.7 (0.40) [56] | 51.11 [56] | >100 [56] | 7.7 [58] a) |
1d | H | H | F | H | 81.1 (0.91) [56] | >100 [56] | 56.65 [56] | - |
1e | H | OH | H | H | 54.1 (0.65) [56] | 56.6 [56] | 66.29 [56] | - |
1f | H | OMe | OMe | H | - | - | - | 5.47 [58] |
1g | H | -OCH2CH2O- | H | 19.2 (0.23) [56] | 19.36 [56] | 21.78 [56] | 81 [58] | |
1h | H | R c) | H | H | - | - | 2 [40] | - |
1i | H | R d) | H | H | - | - | 2 [40] | - |
1j | OH | R e) | H | H | - | - | 10 [40] | - |
1k | H | H | H | Et | slightly more active b)[41] | - | - | - |
1l | H | OH | H | Et | similar to luotonin A [41] | - | - | - |
1m | H | H | H | CF3 | inhibition at 40 μM [59] | - | - | - |
Doxo f) | - | 2.31 [56] | 4.78 [56] | - | ||||
CPT | 83.9 (1) [56] | 2.17 [56] | 5.51 [56] | - |
5.3. Modifications on Rings D and E
R7 | R8 | R9 | R10 | IC50 (μM) | |||||
---|---|---|---|---|---|---|---|---|---|
Galactose [25] | ADR-Res [40] | HeLa [40] | MCF7 [40] | H460 [41] a) | |||||
1aa | H | H | H | H | 0.58 | 5 | 3 | 3 | 7.7 |
1n | H | H | F | H | 9.58 | - | - | - | - |
1o | H | NH2 | H | H | 15.7 | - | - | - | - |
1p | H | H | H | Cl | - | - | - | - | 13 |
1q | H | H | NO2 | H | - | - | - | - | 23 |
1r | CH3 | H | H | H | - | - | - | - | 7 |
1s | H | H | Cl | H | - | - | - | - | 45 |
1t | H | H | OH | H | - | - | - | - | 3.8 |
1u | Cl | H | H | H | - | 13 | >10 | 10 | - |
1v | NH2 | H | H | H | - | 3 | 2 | 2 | - |
1w | OCH3e | H | H | H | - | >20 | 12 | >20 | 11 |
1x | H | OH | OH | H | - | >20 | 6 | 10 | - |
46 | 11.8 | - | - | - | - | ||||
47 | 91.4 | - | - | - | - | ||||
CPT | 0.86 | 0.01 | 0.01 | 0.01 | - | ||||
SN-38 | - | - | - | - | 0.21 b) |
5.4. 14-Azacamptothecin – A Hybrid Molecule of Luotonin A and Camptothecin
Compound | Concentration (μM) | Inhibition on growth medium (%) | Topo I dependent cytotoxicity (IC50, μM)b) | |
---|---|---|---|---|
Raffinose | Galactose | |||
CPT | 1.0 | 0 | 74 | 0.15 |
Luotonin A (1aa) | 1.0 | 0 | 36 | |
0.5 | 0 | 23 | ||
14-aza-CPT (53a) | 2.0 | 0 | 46 | >10 |
53b | 1.28 |
6. Conclusions and Perspectives
Acknowledgements
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- Sample Availability: Samples of the compounds 1d,e,g are available from the authors.
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Liang, J.L.; Cha, H.C.; Jahng, Y. Recent Advances in the Studies on Luotonins. Molecules 2011, 16, 4861-4883. https://doi.org/10.3390/molecules16064861
Liang JL, Cha HC, Jahng Y. Recent Advances in the Studies on Luotonins. Molecules. 2011; 16(6):4861-4883. https://doi.org/10.3390/molecules16064861
Chicago/Turabian StyleLiang, Jing Lu, Hyo Chang Cha, and Yurngdong Jahng. 2011. "Recent Advances in the Studies on Luotonins" Molecules 16, no. 6: 4861-4883. https://doi.org/10.3390/molecules16064861