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