Chem. J. Chinese Universities ›› 2014, Vol. 35 ›› Issue (6): 1181.doi: 10.7503/cjcu20140066
• Organic Chemistry • Previous Articles Next Articles
LI Xiaoliu1,*(), MA Donglai1, YANG Hailong1, TAN Guanhai1, DU Huiru2, WANG Kerang1, ZHANG Pingzhu1, CHEN Hua1
Received:
2014-01-20
Online:
2014-06-10
Published:
2014-02-25
Contact:
LI Xiaoliu
E-mail:lixl@hbu.cn
Supported by:
TrendMD:
LI Xiaoliu, MA Donglai, YANG Hailong, TAN Guanhai, DU Huiru, WANG Kerang, ZHANG Pingzhu, CHEN Hua. Synthesis, Antitumor Activity and DNA Binding of cridine-polyamine Conjugates†[J]. Chem. J. Chinese Universities, 2014, 35(6): 1181.
Scheme 1 Synthesis of acridine-polyamine conjugatesReagents and conditions: a. ClCH2CH2COCl, reflux, 4 h; b. H2NCH2(CH2NHCH2)nCH2NH2(n=1-3), EtOH, NaI, reflux, 5 h; c. MeOH, Boc2O, r.t., 2 h; d. 36%(mass fraction) HCl/EtOH(volume ratio: 1∶3); e. H2NCH2(CH2)nNH2(n=1-3), EtOH, NaI, reflux, 5 h, 36%(mass fraction) HCl/EtOH(volume ratio: 1∶3).
Compd. | IC50/(μmol·L-1) | ||
---|---|---|---|
HeLa | A549 | K562 | |
ACP1 | 113.37±11.18 | 32.17±3.14 | 16.55±0.98 |
ACP2 | 3.56±0.07 | 2.54±0.02 | 1.27±0.06 |
ACP3 | 54.05±2.66 | 17.47±1.28 | 15.92±0.89 |
ACP4 | 23.10±1.63 | 9.44±0.50 | 12.53±1.15 |
ACP5 | 19.29±0.42 | 11.30±0.12 | 7.46±1.14 |
ACP6 | 30.74±2.65 | 20.17±1.23 | 10.60±1.40 |
Cis-platin | 9.31±1.31 | 27.57±1.85 | 16.90±1.36 |
Table 1 Cytotoxicity data of ACP1-ACP6
Compd. | IC50/(μmol·L-1) | ||
---|---|---|---|
HeLa | A549 | K562 | |
ACP1 | 113.37±11.18 | 32.17±3.14 | 16.55±0.98 |
ACP2 | 3.56±0.07 | 2.54±0.02 | 1.27±0.06 |
ACP3 | 54.05±2.66 | 17.47±1.28 | 15.92±0.89 |
ACP4 | 23.10±1.63 | 9.44±0.50 | 12.53±1.15 |
ACP5 | 19.29±0.42 | 11.30±0.12 | 7.46±1.14 |
ACP6 | 30.74±2.65 | 20.17±1.23 | 10.60±1.40 |
Cis-platin | 9.31±1.31 | 27.57±1.85 | 16.90±1.36 |
Fig.2 UV-Vis spectral changes of compounds ACP1(A), ACP2(B), ACP3(C) and ACP6(D) at the concentration of 1.0×10-5 mol/L upon addition of Ct-DNA in phosphate buffer(10 mmol/L, pH=7.4) containing 50 mmol/L NaCl at 25 ℃The arrows show the concentration increasing of Ct-DNA(0-166 μmol/L). Insets are the fitting plots of the binding constants for ACP1, ACP2, ACP3 and ACP6 with Ct-DNA obtained at the maximum absorption band.
Fig.3 Fluorescence spectral changes of compounds ACP1(A), ACP2(B), ACP3(C) and ACP6(D) at the concentration of 1.0×10-5 mol/L upon addition of Ct-DNA in phosphate buffer(10 mmol/L, pH=7.4) containing 50 mmol/L NaCl at 25 ℃The arrows show the concentration increasing of Ct-DNA(0-166 μmol/L). λex=382.5 nm. Insets show the fluorescence changes for ACP1, ACP2, ACP3 and ACP6 with Ct-DNA obtained at the maximum fluorescence band.
Fig.4 CD spectra of Ct-DNA(5.0×10-5 mol/L) in the absence and presence of ACP1, ACP2, ACP3 and ACP6(2.0×10-5 mol/L) in phosphate buffer(10 mmol/L, pH=7.4) containing 50 mmol/L NaCl at 25 ℃a. Ct-DNA; b. ACP4+Ct-DNA; c. ACP3+Ct-DNA;d. ACP2+Ct-DNA; e. ACP1+Ct-DNA.
Fig.5 DNA melting curves for Ct-DNA(5.0×10-5 mol/L) in the absence and presence of ACP1, ACP2, ACP3 and ACP6 with concentration of 5.0×10-6 mol/L in phosphate buffer(10 mmol/L, pH=7.4) containing 50 mmol/L NaCl
Compd. | Ct-DNA | ACP1 | ACP2 | ACP3 | ACP6 |
---|---|---|---|---|---|
Tm/℃ | 78.35 | 80.25 | 81.76 | 81.23 | 81.42 |
ΔTm/℃ | 1.90 | 3.41 | 2.88 | 3.07 |
Table 2 Average Tm and ΔTm for Ct-DNA in the absence and presence of ACP1, ACP2, ACP3 and ACP6
Compd. | Ct-DNA | ACP1 | ACP2 | ACP3 | ACP6 |
---|---|---|---|---|---|
Tm/℃ | 78.35 | 80.25 | 81.76 | 81.23 | 81.42 |
ΔTm/℃ | 1.90 | 3.41 | 2.88 | 3.07 |
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