Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity
Abstract
:1. Introduction
1.1. Antitumoral Activity of Cryptolepine
1.2. Antitumoral Activity of Neocryptolepines and Isocryptolepines
2. Compare Study
3. Conclusions
Funding
Conflicts of Interest
References
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No. | Substituent | IC50 μM | |||||||
---|---|---|---|---|---|---|---|---|---|
R1 | R2 | R3 | R4 | R5 | BALB/3T3 | MV4-11 | A549 | HCT116 | |
7a | H | NH(CH2)3NH2 | H | Me | - | 0.884 ± 0.115 | 0.066 ± 0.023 | 0.205 ± 0.079 | 0.302 ± 0.056 |
7b | Cl | NH(CH2)3NH2 | H | Me | - | 0.401 ± 0.015 | 0.068 ± 0.018 | 0.761 ± 0.169 | 0.195 ± 0.044 |
7c | Br | NH(CH2)3NH2 | H | Me | - | 0.869 ± 0.018 | 0.012 ± 0.002 | 0.543 ± 0.256 | 0.274 ± 0.050 |
7d | OMe | NH(CH2)3NH2 | H | Me | - | 0.978 ± 0.021 | 0.102 ± 0.021 | 0.407 ± 0.117 | 0.155 ± 0.042 |
7e | Cl | NHCH2CH(OH)CH2NH2 | H | Me | - | 0.896 ± 0.042 | 0.042 ± 0.014 | 0.197 ± 0.028 | 0.138 ± 0.050 |
7f | Br | NHCH2CH(OH)CH2NH2 | H | Me | - | 0.864 ± 0.015 | 0.057 ± 0.015 | 0.190 ± 0.027 | 0.117 ± 0.055 |
7g | H | NH(CH2)3NH2 | COOMe | Me | - | 0.933 ± 0.047 | 0.044 ± 0.011 | 0.820 ± 0.456 | 0.176 ± 0.055 |
7h | Br | NH(CH2)3NH2 | COOMe | Me | - | 0.773 ± 0.023 | 0.050 ± 0.016 | 0.302 ± 0.138 | 0.164 ± 0.070 |
7i | Cl | NH(CH2)3NH2 | COOMe | Me | - | 0.833 ± 0.030 | 0.056 ± 0.035 | 0.194 ± 0.063 | 0.116 ± 0.078 |
7j | Cl | NH(CH2)3NH2 | Br | Me | - | 0.834 ± 0.067 | 0.076 ± 0.034 | 0.464 ± 0.011 | 0.284 ± 0.142 |
8 | Cl | NH(CH2)2NH2 | H | - | Me | 0.437 ± 0.400 | 0.456 ± 0.123 | 8.282 ± 0.585 | 6.989 ± 1.416 |
9 | OMe | NH(CH2)2NH2 | H | - | - | 6.87 ± 1.74 | 0.12 ± 0.07 | 9.29 ± 1.10 | 1.93 ± 0.24 |
Cisplatin | 8.53 ± 3.53 | 2.36 ± 0.68 | 7.83 ± 2.60 | 3.47 ± 0.77 | |||||
Doxorubicin HCl | 1.08 ± 0.03 | 0.006 ± 0.002 | 0.33 ± 0.10 | 0.39 ± 0.10 |
No. | Substituent | IC50 μM | |||||
---|---|---|---|---|---|---|---|
R1 | R2 | R3 | BALB/3T3 | MV4-11 | A549 | HCT116 | |
10a | H | NH(CH2)3NH2 | H | 1.05 ± 0.13 | 0.12 ± 0.01 | 0.17 ± 0.05 | 0.26 ± 0.11 |
10b | OMe | NH(CH2)3NH2 | H | 0.31 ± 0.03 | 0.12 ± 0.05 | 0.16 ± 0.03 | 0.07 ± 0.03 |
10c | NO2 | NH(CH2)3NH2 | H | 0.36 ± 0.15 | 0.15 ± 0.06 | 0.35 ± 0.22 | 0.10 ± 0.02 |
10d | H | NH(CH2)3NH2 | Me | 0.95 ± 0.24 | 0.11 ± 0.04 | 0.18 ± 0.03 | 0.06 ± 0.02 |
10e | NO2 | NH(CH2)3NH2 | Me | 0.08 ± 0.02 | 0.05 ± 0.01 | 0.11 ± 0.07 | 0.01 ± 0.00 |
10f | H | NH(CH2)3NH(CH3)2 | H | 1.18 ± 0.20 | 0.41 ± 0.31 | 0.87 ± 0.27 | 0.55 ± 0.17 |
10g | Cl | NH(CH2)3NH(CH3)2 | Me | 0.82 ± 0.08 | 0.08 ± 0.03 | 0.57 ± 0.31 | 0.10 ± 0.02 |
Compound | MDA-MB-453 IC50(μM) | WiDr IC50(μM) | SKOv3 IC50(μM) |
---|---|---|---|
Neocryptolepine | 7.48 ± 4.42 | N.T. | N.T. |
7a | 0.50 ± 0.24 | 0.64 ± 0.13 | 2.7 ± 0.42 |
7d | 0.20 ± 0.09 | 0.37 ± 0.07 | 1.3 ± 0.18 |
Cisplatin | 7.6 ± 0.7 a | 8.84 ± 0.52 c | 18.2 ± 0.1 d |
Doxorubicin | 0.086 ± 0.006 b | 0.089 e | 0.52 |
No. | Substituent | IC50 μM | ||||
---|---|---|---|---|---|---|
Compounds | R1 | C11-Substituent | MV4-11 | BALB/3T3 | A549 | HCT116 |
Cisplatin | - | 2.820 ± 0.450 | 8.700 ± 0.097 | 9.870 ± 2.400 | 8.500 ± 0.540 | |
Doxorubicin HCl | - | 0.006 ± 0.002 | 1.078 ± 0.033 | 0.329 ± 0.097 | 0.390 ± 0.098 | |
2a | H | Cl | 1.312 ± 0.262 | - | - | - |
2b | Br | Cl | 0.810 ± 0.145 | - | - | - |
7l | H | | 0.150 ± 0.060 | 4.789 ± 2.018 | 1.512 ± 0.198 | 1.262 ± 0.361 |
7m | Cl | | 0.119 ± 0.043 | 9.131 ± 0.844 | 1.455 ± 0.168 | 1.373 ± 0.351 |
7n | Me | | 0.105 ± 0.027 | 10.558 ± 0.330 | 1.795 ± 0.270 | 2.370 ± 0.481 |
7o | Cl | | 0.103 ± 0.014 | 1.018 ± 0.017 | 1.269 ± 0.118 | 1.204 ± 0.283 |
7p | Br | | 0.078 ± 0.020 | 0.939 ± 0.018 | 0.988 ± 0.164 | 0.842 ± 0.367 |
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Tissue of Origin | Cell Line | 7d | 7k | 7q | ||||||
GI 50 (µM) | TGI (µM) | IC50 (µM) | GI 50 (µM) | TGI (µM) | IC50 (µM) | GI 50 (µM) | TGI (µM) | IC50 (µM) | ||
Breast | HBC-4 | 0.06 | 0.80 | 9.5 | 0.08 | 0.61 | 6.1 | 1.3 | 4.3 | 19 |
BSY-1 | 0.11 | 0.30 | 0.82 | 0.12 | 0.35 | 3.5 | 2.0 | 5.2 | 20 | |
HBC-5 | 0.06 | 0.33 | 3.4 | 0.09 | 0.41 | 4.1 | 0.86 | 10 | 53 | |
MCF-7 | 0.04 | 0.24 | 17 | 0.03 | 0.31 | 3.1 | 0.87 | 7.9 | 44 | |
MDA-MB-231 | 0.08 | 0.33 | 6.9 | 0.07 | 0.34 | 3.4 | 0.50 | 4.1 | 44 | |
CNS | U251 | 0.04 | 0.47 | 17 | 0.05 | 0.55 | 7.9 | 0.7 | 13 | 58 |
SF-268 | 0.05 | 0.59 | 26 | 0.06 | 0.75 | 4.7 | 0.94 | 14 | 76 | |
SF-295 | 0.10 | 0.81 | 14 | 0.11 | 0.55 | 2.9 | 1.3 | 14 | 49 | |
SF-539 | 0.05 | 0.20 | 0.60 | 0.07 | 0.23 | 0.63 | 0.7 | 3.9 | 22 | |
SNB-75 | 0.13 | 0.34 | 0.91 | 0.15 | 0.38 | 0.93 | 3.3 | 15 | 42 | |
SNB-78 | 0.12 | 0.78 | 25 | 0.20 | 0.98 | 5.2 | 2.9 | 20 | 62 | |
Colon | HCC2998 | 0.05 | 0.22 | 0.74 | 0.07 | 0.23 | 0.69 | 1.0 | 2.9 | 8.0 |
KM-12 | 0.06 | 0.64 | 23 | 0.09 | 0.59 | 4.6 | 0.72 | 7.0 | 64 | |
HT-29 | 0.04 | 0.54 | 24 | 0.06 | 0.64 | 28 | 0.56 | 5.6 | 46 | |
HCT-15 | 0.72 | 6.9 | 50 | 1.0 | 3.7 | 100 | 0.58 | 5.8 | 49 | |
HCT-116 | 0.04 | 0.57 | 22 | 0.04 | 0.80 | 5.1 | 0.43 | 2.3 | 15 | |
Lung | NCI-H23 | 0.06 | 0.28 | 1.8 | 0.07 | 0.36 | 2.5 | 1.2 | 4.8 | 98 |
NCI-H226 | 0.08 | 0.49 | 25 | 0.09 | 0.63 | 6.2 | 0.74 | 4.8 | 44 | |
NCI-H522 | 0.04 | 0.20 | 0.71 | 0.04 | 0.18 | 0.57 | 0.42 | 1.8 | 5.5 | |
NCI-H460 | 0.05 | 0.27 | 3.4 | 0.05 | 0.23 | 1.7 | 0.45 | 2.6 | 20 | |
A549 | 0.06 | 0.23 | 0.85 | 0.05 | 0.26 | 1.9 | 0.68 | 2.5 | 8.3 | |
DMS273 | 0.04 | 0.18 | 0.70 | 0.05 | 0.18 | 0.61 | 0.42 | 1.6 | 4.7 | |
DMS114 | 0.08 | 0.26 | 0.72 | 0.10 | 0.33 | 1.10 | 1.1 | 3.7 | 18 | |
Melanoma | LOX-IMVI | 0.03 | 0.11 | 1.1 | 0.03 | 0.11 | 0.75 | 0.31 | 1.5 | 7.6 |
Ovarian | OVCAR-3 | 0.06 | 0.28 | 8.0 | 0.05 | 0.30 | 42 | 0.64 | 4.6 | 82 |
OVCAR-4 | 0.04 | 0.15 | 0.48 | 0.04 | 0.16 | 59 | 0.52 | 2.7 | 19 | |
OVCAR-5 | 0.05 | 0.35 | 9.5 | 0.05 | 0.26 | 42 | 0.56 | 3.1 | 32 | |
OVCAR-8 | 0.05 | 0.33 | 23 | 0.05 | 0.43 | 100 | 0.48 | 3.4 | 100 | |
SK-OV-3 | 0.13 | 1.0 | 20 | 0.13 | 1.2 | 54 | 1.2 | 7.4 | 51 | |
Renal | RXF-631L | 0.27 | 1.4 | 7.4 | 0.19 | 0.67 | 3.0 | 1.1 | 3.0 | 18 |
ACHN | 0.27 | 2.1 | 20 | 0.25 | 2.2 | 10 | 0.7 | 7.1 | 51 | |
Stomach | St-4 | 0.06 | 0.43 | 3.8 | 0.12 | 0.60 | 3.7 | 0.72 | 4.9 | 44 |
MKN1 | 0.09 | 0.38 | 12 | 0.11 | 0.47 | 3.1 | 1.1 | 3.6 | 14 | |
MKN7 | 0.04 | 0.34 | 23 | 0.06 | 0.48 | 36 | 0.9 | 8.0 | 69 | |
MKN28 | 0.05 | 0.9 | 37 | 0.05 | 1.1 | 58 | 0.55 | 12 | 100 | |
MKN45 | 0.05 | 1.0 | 28 | 0.05 | 1.1 | 8.0 | 0.44 | 6.2 | 100 | |
MKN74 | 0.05 | 1.0 | 52 | 0.06 | 0.94 | 8.0 | 0.56 | 6.8 | 100 | |
Prostate | DU145 | 0.1 | 0.34 | 17 | 0.09 | 0.43 | 3.3 | 1.2 | 4.0 | 22 |
PC-3 | 0.16 | 1.3 | 70 | 0.16 | 1.3 | 22 | 2.0 | 12 | 56 |
Compound | R1 | R2 | R3 | MV4-11 | A549 | HCT116 | BALB/3T3 |
---|---|---|---|---|---|---|---|
11a | Cl | CH3 | CH3 | 0.072 ± 0.022 | 4.555 ± 2.086 | 0.893 ± 0.397 | 6.423 ± 0.996 |
11b | CO2Me | CH3 | CH3 | 0.075 ± 0.001 | 5.060 ± 0.911 | 2.206 ± 0.687 | 5.945 ± 1.163 |
12 | CO2Me | H | H | 0.086 ± 0.020 | 0.649 ± 0.080 | 0.130 ± 0.014 | 0.768 ± 0.155 |
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Wang, N.; Świtalska, M.; Wang, L.; Shaban, E.; Hossain, M.I.; El Sayed, I.E.T.; Wietrzyk, J.; Inokuchi, T. Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity. Molecules 2019, 24, 2121. https://doi.org/10.3390/molecules24112121
Wang N, Świtalska M, Wang L, Shaban E, Hossain MI, El Sayed IET, Wietrzyk J, Inokuchi T. Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity. Molecules. 2019; 24(11):2121. https://doi.org/10.3390/molecules24112121
Chicago/Turabian StyleWang, Ning, Marta Świtalska, Li Wang, Elkhabiry Shaban, Md Imran Hossain, Ibrahim El Tantawy El Sayed, Joanna Wietrzyk, and Tsutomu Inokuchi. 2019. "Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity" Molecules 24, no. 11: 2121. https://doi.org/10.3390/molecules24112121
APA StyleWang, N., Świtalska, M., Wang, L., Shaban, E., Hossain, M. I., El Sayed, I. E. T., Wietrzyk, J., & Inokuchi, T. (2019). Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity. Molecules, 24(11), 2121. https://doi.org/10.3390/molecules24112121