高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (6): 1100.doi: 10.7503/cjcu20141145
刘丹1, 胡秀芳1, 郑艳艳1, 潘鹤1, 罗舒维1, 洪芳1, 赵文娜1, 姜美红1, 祝云辉1, 邵敬伟1, 王文峰1,2()
收稿日期:
2014-12-31
出版日期:
2015-06-10
发布日期:
2015-05-15
作者简介:
联系人简介: 王文峰, 男, 博士, 教授, 主要从事药物合成研究. E-mail:基金资助:
LIU Dan1, HU Xiufang1, ZHENG Yanyan1, PAN He1, LUO Shuwei1, HONG Fang1, ZHAO Wenna1, JIANG Meihong1, ZHU Yunhui1, SHAO Jingwei1, WANG Wenfeng1,2,*()
Received:
2014-12-31
Online:
2015-06-10
Published:
2015-05-15
Contact:
WANG Wenfeng
E-mail:wangwf@fzu.edu.cn
Supported by:
摘要:
合成了7个大黄素季铵盐、 2个芦荟大黄素季铵盐、 1个水溶性大黄素季铵盐和1个α-萘酚醌苯基甲烷季铵盐化合物, 并测试了其抗癌活性. 含有1条长碳链的大黄素季铵盐的抗癌活性很低, 但是含有2条长碳链的大黄素和芦荟大黄素季铵盐的抗癌活性较好. 用亲水性的长链替代季铵盐中亲脂性的长碳链会导致大黄素季铵盐失去抗癌活性. α-萘酚醌苯基甲烷季铵盐显示了中等的抗癌活性, 表明在具有电子传递能力的分子中引入亲脂性的长碳链季铵盐可以增加其抗癌活性.
TrendMD:
刘丹, 胡秀芳, 郑艳艳, 潘鹤, 罗舒维, 洪芳, 赵文娜, 姜美红, 祝云辉, 邵敬伟, 王文峰. 蒽醌类亲脂性阳离子的合成及抗癌活性. 高等学校化学学报, 2015, 36(6): 1100.
LIU Dan, HU Xiufang, ZHENG Yanyan, PAN He, LUO Shuwei, HONG Fang, ZHAO Wenna, JIANG Meihong, ZHU Yunhui, SHAO Jingwei, WANG Wenfeng. Synthesis of Lipiophilic Cations of Anthraquinone and Their Anticancer Activities†. Chem. J. Chinese Universities, 2015, 36(6): 1100.
Compd. | Appearance | Yield(%) | m. p./℃ | Elemental analysis(%, calcd.) | LC-MS, m/z | HRMS(Calcd.), m/z | ||
---|---|---|---|---|---|---|---|---|
C | H | N | ||||||
2a | Yellow solid | 68.3 | 143—144 | 60.71(60.940) | 7.08(7.230) | 2.27(2.45) | 482.5 | |
2b | Yellow solid | 66.5 | 89—90 | 62.53(62.520) | 8.41(8.510) | 2.06(1.97) | 494.4 | |
2c | Yellow solid | 63.5 | 75—76 | 63.54(63.520) | 8.50(8.600) | 1.91(1.95) | 608.8 | |
3 | Yellow solid | 55.0 | 161—163 | 433.2 | 433.0657(433.0645) | |||
4a | Yellow solid | 50.0 | 65—67 | 61.66(61.440) | 8.66(8.680) | 2.00(1.89) | 608.6 | |
4b | Yellow solid | 48.5 | 64—66 | 59.48(59.540) | 8.84(8.990) | 1.61(1.74) | 636.5 | |
4c | Yellow solid | 68.9 | 60—62 | 62.91(63.140) | 8.96(9.080) | 1.77(1.75) | 664.6 | |
4d | Yellow solid | 62.7 | 60—61 | 67.65(67.460) | 9.36(9.350) | 1.43(1.71) | 720.7 | |
6 | Orange solid | 72.1 | 72—73 | 331.1 | 330.9619(330.9611) | |||
7a | Red solid | 67.3 | 80—81 | 64.54(64.310) | 7.86(7.930) | 2.65(2.34) | 508.6 | |
7b | Red solid | 68.2 | 73—74 | 63.49(63.440) | 8.11(8.300) | 1.93(2.18) | 536.4 | |
8 | Colorless liquid | 55.6 | 296.2 | 296.2068(296.2068) | ||||
9 | Yellow liquid | 35.6 | 606.3 | 606.2914(606.2906) | ||||
10 | Red solid | 75.6 | 56—57 | 509.2 | 509.1116(509.1111) | |||
11 | Red solid | 53.6 | 57—59 | 684.6 | 684.4768(684.4775) |
Table 1 Appearance, yields, elemental analysis, LC-MS and HRMS data for compounds 2—4 and 6—11
Compd. | Appearance | Yield(%) | m. p./℃ | Elemental analysis(%, calcd.) | LC-MS, m/z | HRMS(Calcd.), m/z | ||
---|---|---|---|---|---|---|---|---|
C | H | N | ||||||
2a | Yellow solid | 68.3 | 143—144 | 60.71(60.940) | 7.08(7.230) | 2.27(2.45) | 482.5 | |
2b | Yellow solid | 66.5 | 89—90 | 62.53(62.520) | 8.41(8.510) | 2.06(1.97) | 494.4 | |
2c | Yellow solid | 63.5 | 75—76 | 63.54(63.520) | 8.50(8.600) | 1.91(1.95) | 608.8 | |
3 | Yellow solid | 55.0 | 161—163 | 433.2 | 433.0657(433.0645) | |||
4a | Yellow solid | 50.0 | 65—67 | 61.66(61.440) | 8.66(8.680) | 2.00(1.89) | 608.6 | |
4b | Yellow solid | 48.5 | 64—66 | 59.48(59.540) | 8.84(8.990) | 1.61(1.74) | 636.5 | |
4c | Yellow solid | 68.9 | 60—62 | 62.91(63.140) | 8.96(9.080) | 1.77(1.75) | 664.6 | |
4d | Yellow solid | 62.7 | 60—61 | 67.65(67.460) | 9.36(9.350) | 1.43(1.71) | 720.7 | |
6 | Orange solid | 72.1 | 72—73 | 331.1 | 330.9619(330.9611) | |||
7a | Red solid | 67.3 | 80—81 | 64.54(64.310) | 7.86(7.930) | 2.65(2.34) | 508.6 | |
7b | Red solid | 68.2 | 73—74 | 63.49(63.440) | 8.11(8.300) | 1.93(2.18) | 536.4 | |
8 | Colorless liquid | 55.6 | 296.2 | 296.2068(296.2068) | ||||
9 | Yellow liquid | 35.6 | 606.3 | 606.2914(606.2906) | ||||
10 | Red solid | 75.6 | 56—57 | 509.2 | 509.1116(509.1111) | |||
11 | Red solid | 53.6 | 57—59 | 684.6 | 684.4768(684.4775) |
Compd. | 1H NMR(400 MHz, CDCl3), δ | 13C NMR(400 MHz, CDCl3), δ |
---|---|---|
2a | 8.30(s, 1H, ArH), 7.74(s, 1H, ArH), 7.23(d, J=2.0 Hz, 1H, ArH), 6.74(d, J=2.0 Hz, 1H, ArH), 5.30(s, 2H, ArCH2N), 4.13(s, 3H, OCH3), 3.96(s, 6H, 2×OCH3), 3.58(s, 2H, NCH2), 3.38(s, 6H, 2×NCH3), 1.88(m, 2H, NCH2CH2), 1.39—1.26[m, 12H, (CH2)6], 0.87(t, J=6.8 Hz, 3H, CH3) | 183.0, 180.7, 164.1, 161.8, 160.2, 135.8, 134.7, 132.8, 124.9, 124.1, 121.6, 117.9, 105.3, 102.2, 66.2, 64.7, 57.9, 56.4, 55.9, 50.2, 31.7, 29.3, 29.2, 29.0, 26.3, 23.0, 22.6, 21.8, 14.0 |
2b | 8.60(s, 1H, ArH), 7.67(s, 1H, ArH), 7.32(d, J=2.0 Hz, 1H, ArH), 6.82(d, J=2.0 Hz, 1H, ArH), 5.13(s, 2H, ArCH2N), 4.19(s, 3H, OCH3), 4.00(s, 3H, OCH3), 3.98(s, 3H, OCH3), 3.48(t, J=5.5 Hz, 4H, CH2NCH2), 3.22(s, 3H, NCH3), 1.87—1.49(m, 4H, 2×NCH2CH2), 1.50—1.28[m, 24H, 2×(CH2)6], 0.91(t, J=7.0 Hz, 6H, 2×CH3) | 183.2, 180.8, 164.1, 161.8, 160.3, 135.8, 134.6, 132.7, 124.9, 124.6, 121.0, 118.1, 105.4, 102.1, 64.0, 60.9, 58.4, 58.2, 56.4, 55.9, 47.9, 31.7, 29.3, 29.2, 29.1, 26.3, 22.6, 14.0 |
2c | 8.49(s, 1H, ArH), 7.67(d, J=1.2 Hz, 1H, ArH), 7.29(s, 1H, ArH), 6.78(d, J=2.0 Hz, 1H, ArH), 5.24(s, 2H, ArCH2N), 4.16(s, 3H, OCH3), 3.97(s, 6H, 2×OCH3), 3.45(t, J=8.0 Hz, 4H, CH2NCH2), 3.30(s, 3H, NCH3), 1.86—1.80(m, 4H, 2×NCH2CH2), 1.41—1.27[m, 26H, (CH2)6, (CH2)7], 0.89(t, J=6.8 Hz, 6H, 2×CH3) | 183.2, 180.9, 164.1, 161.8, 160.3, 135.9, 134.6, 132.7, 124.9, 124.6, 121.0, 118.1, 105.4, 102.1, 64.1, 60.8, 58.1, 56.4, 55.9, 48.0, 31.8, 31.7, 29.3, 29.2, 29.1, 26.3, 22.6, 14.0 |
3 | 7.84(d, J=1.2 Hz, 1H, ArH), 7.33(d, J=2.0 Hz, 1H, ArH), 7.33(d, J=1.2 Hz, 1H, ArH), 6.79(d, J=2.0 Hz, 1H, ArH), 4.53(s, 2H, ArCH2Br), 4.29(q, J=5.6 Hz, 2H, ArOCH2CH3), 4.23(q, J=5.6 Hz, 4H, 2×ArOCH2CH3), 1.58(t, J=5.6 Hz, 6H, 2×ArOCH2CH3), 1.51(t, J=5.6 Hz, 3H, ArOCH2CH3) | |
4a | 8.38(s, 1H, ArH), 7.66(s, 1H, ArH), 7.25(d, J=2.4 Hz, 1H, ArH), 6.75(d, J=2.4 Hz, 1H, ArH), 5.22(s, 2H, ArCH2N), 4.42(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.23—4.20(m, 4H, 2×ArOCH2CH3), 3.45(m, 4H, 2×NCH2(CH2)6CH3), 3.29(s, 3H, ArNCH3), 1.82(m, 4H, 2×NCH2CH2C6H13), 1.58—1.52(m, 6H, 2×ArOCH2CH3), 1.47(t, J=6.8 Hz, 3H, ArOCH2CH3), 1.39—1.28[m, 20H, 2×(CH2)5], 0.89[t, J=6.8 Hz, 6H, 2×N(CH2)7CH3] | 183.5, 180.3, 163.3, 161.2, 159.6, 135.9, 134.8, 132.5, 125.4, 125.1, 125.8, 118.3, 106.9, 102.6, 66.6, 65.2, 64.1, 60.8, 31.6, 29.0, 26.3, 14.4, 13.9 |
4b | 8.29(s, 1H, ArH), 7.67(s, 1H, ArH), 7.22(d, J=2.4 Hz, 1H, ArH), 6.73(d, J=2.4 Hz, 1H, ArH), 5.19(s, 2H, ArCH2N), 4.39(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.17(m, 4H, 2×ArOCH2CH3), 3.45—3.40(m, 4H, 2×NCH2C8H17), 3.26(s, 3H, NCH3), 1.81(m, 4H, 2×NCH2CH2C7H15), 1.55—1.51(m, 6H, 2×ArOCH2CH3), 1.45(t, J=6.8 Hz, 3H, ArOCH2CH3), 1.36—1.24[m, 24H, 2×(CH2)6], 0.86(t, J=6.8 Hz, 6H, 2×CH3) | 183.4, 180.3, 163.1, 161.1, 159.5, 135.7, 134.8, 132.6, 125.2, 125.1, 121.0, 118.3, 106.9, 102.7, 66.5, 65.1, 64.2, 61.0, 31.8, 29.3, 22.6, 14.6, 14.0 |
4c | 8.34(s, 1H, ArH), 7.66(s, 1H, ArH ), 7.23(d, J=2.4 Hz, 1H, ArH), 6.74(d, J=2.4 Hz, 1H, ArH), 5.18(s, 2H, ArCH2N), 4.39(q, J=5.6 Hz, 2H, ArOCH2CH3), 4.19—4.14(m, 4H, 2×ArOCH2CH3), 3.42[m, 4H, 2×NCH2(CH2)8CH3], 3.27(s, 3H, ArCH2NCH3), 1.81(m, 4H, 2×NCH2CH2C8H17), 1.55—1.52(m, 6H, 2×ArOCH2CH3), 1.46(t, J=5.6 Hz, 3H, ArOCH2CH3), 1.36—1.24[m, 28H, 2×(CH2)7CH3], 0.86[t, J=6.4 Hz, 6H, 2×N(CH2)9CH3] | 183.5, 180.3, 163.1, 161.2, 159.7, 135.7, 134.9, 125.1, 118.3, 102.8, 66.5, 65.4, 64.1, 60.9, 31.8, 29.2, 26.3, 22.4, 14.6, 14.0 |
4d | 8.37(s, 1H, ArH), 7.66(s, 1H, ArH ), 7.26(d, J=2.4 Hz, 1H, ArH), 6.77(d, J=2.4 Hz, 1H, ArH), 5.17(s, 2H, ArCH2N), 4.40(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.23—4.17(m, 4H, 2×ArOCH2CH3), 3.45—3.41[m, 4H, NCH2(CH2)10CH3], 3.28(s, 3H, NCH3), 1.80(m, 4H, 2×NCH2CH2C10H21), 1.58—1.54(m, 6H, ArOCH2CH3), 1.47(t, J=7.2 Hz, 3H, ArOCH2CH3), 1.39—1.26[m, 36H, 2×(CH2)9CH3], 0.88(t, J=6.4 Hz, 6H, 2×CH3) | 183.5, 180.5, 163.3, 161.1, 159.6, 135.8, 134.8, 132.4, 130.9, 128.8, 125.3, 125.1, 120.9, 118.3, 68.2, 66.4, 65.6, 64.2, 32.0, 29.6, 22.5, 14.5, 14.1 |
6 | 12.09(s, 1H, ArOH), 12.06(s, 1H, ArOH), 7.89(d, J=5.2 Hz, 1H, ArH), 7.88(s, 1H, ArH), 7.73(t, J=7.6 Hz, 1H, ArH), 7.36(s, 1H, ArH), 7.35(d, J=6.4 Hz, 1H, ArH), 4.51(s, 2H, ArCH2Br) | |
Compd. | 1H NMR(400 MHz, CDCl3), δ | 13C NMR(400 MHz, CDCl3), δ |
7a | 11.94(s, 1H, ArOH), 11.88(s, 1H, ArOH), 7.94(s, 1H, ArH), 7.83(d, J=7.6 Hz, 1H, ArH), 7.81(s, 1H, ArH), 7.73(t, J=7.6 Hz, 1H, ArH), 7.35(d, J=8.4Hz, 1H, ArH), 5.29(s, 2H, ArCH2N), 3.58—3.45(m, 4H, 2×NCH2C7H15), 3.37(s, 3H, NCH3), 1.93—1.76(m, 4H, 2×NCH2CH2C6H13), 1.48—1.25[m, 20H, 2×(CH2)5CH3], 0.91(t, J=7.2 Hz, 6H, 2×CH3) | 192.1, 180.3, 162.7, 162.3, 137.8, 137.1, 133.5, 132.8, 129.5, 125.1, 123.0, 120.3, 116.4, 115.3, 63.9, 61.2, 48.3, 31.6, 29.12, 29.09, 26.4, 22.6, 14.1 |
7b | 11.98(s, 1H, ArOH), 11.92(s, 1H, ArOH), 7.97(d, J=1.2 Hz, 1H, ArH), 7.86(dd, J=7.6, 1.2 Hz, 1H, ArH), 7.81(d, J=1.6 Hz, 1H, ArH), 7.75(t, J=7.6 Hz, 1H, ArH), 7.37(dd, J=8.4, 1.2 Hz, 1H, ArH), 5.26(s, 2H, ArCH2N), 3.59—3.44(m, 4H, 2×NCH2C8H17), 3.37(s, 3H, NCH3), 1.90—1.74(m, 4H, 2×NCH2CH2C7H15), 1.46—1.25[m, 24H, 2×(CH2)6CH3], 0.90(t, J=7.2 Hz, 6H, 2×CH3) | 192.1, 180.3, 162.7, 162.3, 137.8, 137.1, 133.5, 132.8, 129.6, 125.1, 123.1, 120.3, 116.4, 115.2, 63.7, 61.1, 48.4, 31.8, 29.4, 29.2, 29.1, 26.4, 22.6, 14.1 |
8 | 3.64(s, 16H, 8×OCH2), 3.56(t, J=5.2 Hz, 4H, 2×CH2OH), 3.34(s, 2H, 2×OH), 2.85(s, 3H, CH3), 2.66(t, J=4.4 Hz, 4H, 2×NCH2) | |
9 | 7.52(s, 2H, ArH), 6.27(s, 1H, ArH), 6.19(s, 1H, ArH), 4.70(s, 2H, ArCH2N, Overlapped by peak of water), 4.08—3.92(m, 9H, 3×OCH3), 3.80—3.65(m, 16H, 8×OCH2), 3.62(t, J=4.0 Hz, 4H, 2×CH2OH), 3.60(t, J=4.0 Hz, 4H, 2×NCH2), 3.17(s, 3H, NCH3) | 184.9, 182.3, 165.6, 161.8, 160.0, 138.1, 134.3, 128.7, 127.5, 123.3, 114.1, 107.9, 105.8, 101.3, 83.7, 79.3, 77.9, 72.4, 64.2, 61.8, 60.7, 54.1 |
10 | 7.80—6.32(m, 17H, ArH), 4.23(t, J=6.0 Hz, 2H, OCH2CH2CH2CH2Br), 3.60(t, 2H, J=6.0 Hz, OCH2CH2CH2CH2Br), 2.22—2.17(m, 4H, OCH2CH2CH2CH2Br) | |
11 | 8.26—6.30(m, 17H, ArH), 4.33(t, J=5.2 Hz, 2H, OCH2CH2CH2CH2N), 3.85(t, 2H, J=5.2 Hz, OCH2CH2CH2CH2N), 3.47[m, 4H, N(CH2C7H15)2], 3.40(s, 3H, NCH3), 2.16—2.12(m, 4H, OCH2CH2CH2CH2N), 1.72—1.70[m, 4H, N(CH2CH2C6H13)2], 1.39—1.24[m, 20H, N(C2H4C5H10CH3)2], 0.87[t, J=6.8 Hz, 6H, N(C7H14CH3)2] | 184.6, 155.4, 154.6, 153.6, 144.0, 142.8, 136.2, 133.6, 133.1, 132.4, 132.3, 132.1, 131.9, 131.4, 131.1, 130.2, 129.3, 128.9, 128.4, 127.6, 127.5, 126.3, 126.1, 125.8, 125.6, 122.0, 104.9, 67.0, 61.6, 49.0, 31.6, 29.1, 26.4, 22.5, 14.1 |
Table 2 1H NMR and 13C NMR data for compounds 2—4 and 6—11
Compd. | 1H NMR(400 MHz, CDCl3), δ | 13C NMR(400 MHz, CDCl3), δ |
---|---|---|
2a | 8.30(s, 1H, ArH), 7.74(s, 1H, ArH), 7.23(d, J=2.0 Hz, 1H, ArH), 6.74(d, J=2.0 Hz, 1H, ArH), 5.30(s, 2H, ArCH2N), 4.13(s, 3H, OCH3), 3.96(s, 6H, 2×OCH3), 3.58(s, 2H, NCH2), 3.38(s, 6H, 2×NCH3), 1.88(m, 2H, NCH2CH2), 1.39—1.26[m, 12H, (CH2)6], 0.87(t, J=6.8 Hz, 3H, CH3) | 183.0, 180.7, 164.1, 161.8, 160.2, 135.8, 134.7, 132.8, 124.9, 124.1, 121.6, 117.9, 105.3, 102.2, 66.2, 64.7, 57.9, 56.4, 55.9, 50.2, 31.7, 29.3, 29.2, 29.0, 26.3, 23.0, 22.6, 21.8, 14.0 |
2b | 8.60(s, 1H, ArH), 7.67(s, 1H, ArH), 7.32(d, J=2.0 Hz, 1H, ArH), 6.82(d, J=2.0 Hz, 1H, ArH), 5.13(s, 2H, ArCH2N), 4.19(s, 3H, OCH3), 4.00(s, 3H, OCH3), 3.98(s, 3H, OCH3), 3.48(t, J=5.5 Hz, 4H, CH2NCH2), 3.22(s, 3H, NCH3), 1.87—1.49(m, 4H, 2×NCH2CH2), 1.50—1.28[m, 24H, 2×(CH2)6], 0.91(t, J=7.0 Hz, 6H, 2×CH3) | 183.2, 180.8, 164.1, 161.8, 160.3, 135.8, 134.6, 132.7, 124.9, 124.6, 121.0, 118.1, 105.4, 102.1, 64.0, 60.9, 58.4, 58.2, 56.4, 55.9, 47.9, 31.7, 29.3, 29.2, 29.1, 26.3, 22.6, 14.0 |
2c | 8.49(s, 1H, ArH), 7.67(d, J=1.2 Hz, 1H, ArH), 7.29(s, 1H, ArH), 6.78(d, J=2.0 Hz, 1H, ArH), 5.24(s, 2H, ArCH2N), 4.16(s, 3H, OCH3), 3.97(s, 6H, 2×OCH3), 3.45(t, J=8.0 Hz, 4H, CH2NCH2), 3.30(s, 3H, NCH3), 1.86—1.80(m, 4H, 2×NCH2CH2), 1.41—1.27[m, 26H, (CH2)6, (CH2)7], 0.89(t, J=6.8 Hz, 6H, 2×CH3) | 183.2, 180.9, 164.1, 161.8, 160.3, 135.9, 134.6, 132.7, 124.9, 124.6, 121.0, 118.1, 105.4, 102.1, 64.1, 60.8, 58.1, 56.4, 55.9, 48.0, 31.8, 31.7, 29.3, 29.2, 29.1, 26.3, 22.6, 14.0 |
3 | 7.84(d, J=1.2 Hz, 1H, ArH), 7.33(d, J=2.0 Hz, 1H, ArH), 7.33(d, J=1.2 Hz, 1H, ArH), 6.79(d, J=2.0 Hz, 1H, ArH), 4.53(s, 2H, ArCH2Br), 4.29(q, J=5.6 Hz, 2H, ArOCH2CH3), 4.23(q, J=5.6 Hz, 4H, 2×ArOCH2CH3), 1.58(t, J=5.6 Hz, 6H, 2×ArOCH2CH3), 1.51(t, J=5.6 Hz, 3H, ArOCH2CH3) | |
4a | 8.38(s, 1H, ArH), 7.66(s, 1H, ArH), 7.25(d, J=2.4 Hz, 1H, ArH), 6.75(d, J=2.4 Hz, 1H, ArH), 5.22(s, 2H, ArCH2N), 4.42(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.23—4.20(m, 4H, 2×ArOCH2CH3), 3.45(m, 4H, 2×NCH2(CH2)6CH3), 3.29(s, 3H, ArNCH3), 1.82(m, 4H, 2×NCH2CH2C6H13), 1.58—1.52(m, 6H, 2×ArOCH2CH3), 1.47(t, J=6.8 Hz, 3H, ArOCH2CH3), 1.39—1.28[m, 20H, 2×(CH2)5], 0.89[t, J=6.8 Hz, 6H, 2×N(CH2)7CH3] | 183.5, 180.3, 163.3, 161.2, 159.6, 135.9, 134.8, 132.5, 125.4, 125.1, 125.8, 118.3, 106.9, 102.6, 66.6, 65.2, 64.1, 60.8, 31.6, 29.0, 26.3, 14.4, 13.9 |
4b | 8.29(s, 1H, ArH), 7.67(s, 1H, ArH), 7.22(d, J=2.4 Hz, 1H, ArH), 6.73(d, J=2.4 Hz, 1H, ArH), 5.19(s, 2H, ArCH2N), 4.39(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.17(m, 4H, 2×ArOCH2CH3), 3.45—3.40(m, 4H, 2×NCH2C8H17), 3.26(s, 3H, NCH3), 1.81(m, 4H, 2×NCH2CH2C7H15), 1.55—1.51(m, 6H, 2×ArOCH2CH3), 1.45(t, J=6.8 Hz, 3H, ArOCH2CH3), 1.36—1.24[m, 24H, 2×(CH2)6], 0.86(t, J=6.8 Hz, 6H, 2×CH3) | 183.4, 180.3, 163.1, 161.1, 159.5, 135.7, 134.8, 132.6, 125.2, 125.1, 121.0, 118.3, 106.9, 102.7, 66.5, 65.1, 64.2, 61.0, 31.8, 29.3, 22.6, 14.6, 14.0 |
4c | 8.34(s, 1H, ArH), 7.66(s, 1H, ArH ), 7.23(d, J=2.4 Hz, 1H, ArH), 6.74(d, J=2.4 Hz, 1H, ArH), 5.18(s, 2H, ArCH2N), 4.39(q, J=5.6 Hz, 2H, ArOCH2CH3), 4.19—4.14(m, 4H, 2×ArOCH2CH3), 3.42[m, 4H, 2×NCH2(CH2)8CH3], 3.27(s, 3H, ArCH2NCH3), 1.81(m, 4H, 2×NCH2CH2C8H17), 1.55—1.52(m, 6H, 2×ArOCH2CH3), 1.46(t, J=5.6 Hz, 3H, ArOCH2CH3), 1.36—1.24[m, 28H, 2×(CH2)7CH3], 0.86[t, J=6.4 Hz, 6H, 2×N(CH2)9CH3] | 183.5, 180.3, 163.1, 161.2, 159.7, 135.7, 134.9, 125.1, 118.3, 102.8, 66.5, 65.4, 64.1, 60.9, 31.8, 29.2, 26.3, 22.4, 14.6, 14.0 |
4d | 8.37(s, 1H, ArH), 7.66(s, 1H, ArH ), 7.26(d, J=2.4 Hz, 1H, ArH), 6.77(d, J=2.4 Hz, 1H, ArH), 5.17(s, 2H, ArCH2N), 4.40(q, J=6.8 Hz, 2H, ArOCH2CH3), 4.23—4.17(m, 4H, 2×ArOCH2CH3), 3.45—3.41[m, 4H, NCH2(CH2)10CH3], 3.28(s, 3H, NCH3), 1.80(m, 4H, 2×NCH2CH2C10H21), 1.58—1.54(m, 6H, ArOCH2CH3), 1.47(t, J=7.2 Hz, 3H, ArOCH2CH3), 1.39—1.26[m, 36H, 2×(CH2)9CH3], 0.88(t, J=6.4 Hz, 6H, 2×CH3) | 183.5, 180.5, 163.3, 161.1, 159.6, 135.8, 134.8, 132.4, 130.9, 128.8, 125.3, 125.1, 120.9, 118.3, 68.2, 66.4, 65.6, 64.2, 32.0, 29.6, 22.5, 14.5, 14.1 |
6 | 12.09(s, 1H, ArOH), 12.06(s, 1H, ArOH), 7.89(d, J=5.2 Hz, 1H, ArH), 7.88(s, 1H, ArH), 7.73(t, J=7.6 Hz, 1H, ArH), 7.36(s, 1H, ArH), 7.35(d, J=6.4 Hz, 1H, ArH), 4.51(s, 2H, ArCH2Br) | |
Compd. | 1H NMR(400 MHz, CDCl3), δ | 13C NMR(400 MHz, CDCl3), δ |
7a | 11.94(s, 1H, ArOH), 11.88(s, 1H, ArOH), 7.94(s, 1H, ArH), 7.83(d, J=7.6 Hz, 1H, ArH), 7.81(s, 1H, ArH), 7.73(t, J=7.6 Hz, 1H, ArH), 7.35(d, J=8.4Hz, 1H, ArH), 5.29(s, 2H, ArCH2N), 3.58—3.45(m, 4H, 2×NCH2C7H15), 3.37(s, 3H, NCH3), 1.93—1.76(m, 4H, 2×NCH2CH2C6H13), 1.48—1.25[m, 20H, 2×(CH2)5CH3], 0.91(t, J=7.2 Hz, 6H, 2×CH3) | 192.1, 180.3, 162.7, 162.3, 137.8, 137.1, 133.5, 132.8, 129.5, 125.1, 123.0, 120.3, 116.4, 115.3, 63.9, 61.2, 48.3, 31.6, 29.12, 29.09, 26.4, 22.6, 14.1 |
7b | 11.98(s, 1H, ArOH), 11.92(s, 1H, ArOH), 7.97(d, J=1.2 Hz, 1H, ArH), 7.86(dd, J=7.6, 1.2 Hz, 1H, ArH), 7.81(d, J=1.6 Hz, 1H, ArH), 7.75(t, J=7.6 Hz, 1H, ArH), 7.37(dd, J=8.4, 1.2 Hz, 1H, ArH), 5.26(s, 2H, ArCH2N), 3.59—3.44(m, 4H, 2×NCH2C8H17), 3.37(s, 3H, NCH3), 1.90—1.74(m, 4H, 2×NCH2CH2C7H15), 1.46—1.25[m, 24H, 2×(CH2)6CH3], 0.90(t, J=7.2 Hz, 6H, 2×CH3) | 192.1, 180.3, 162.7, 162.3, 137.8, 137.1, 133.5, 132.8, 129.6, 125.1, 123.1, 120.3, 116.4, 115.2, 63.7, 61.1, 48.4, 31.8, 29.4, 29.2, 29.1, 26.4, 22.6, 14.1 |
8 | 3.64(s, 16H, 8×OCH2), 3.56(t, J=5.2 Hz, 4H, 2×CH2OH), 3.34(s, 2H, 2×OH), 2.85(s, 3H, CH3), 2.66(t, J=4.4 Hz, 4H, 2×NCH2) | |
9 | 7.52(s, 2H, ArH), 6.27(s, 1H, ArH), 6.19(s, 1H, ArH), 4.70(s, 2H, ArCH2N, Overlapped by peak of water), 4.08—3.92(m, 9H, 3×OCH3), 3.80—3.65(m, 16H, 8×OCH2), 3.62(t, J=4.0 Hz, 4H, 2×CH2OH), 3.60(t, J=4.0 Hz, 4H, 2×NCH2), 3.17(s, 3H, NCH3) | 184.9, 182.3, 165.6, 161.8, 160.0, 138.1, 134.3, 128.7, 127.5, 123.3, 114.1, 107.9, 105.8, 101.3, 83.7, 79.3, 77.9, 72.4, 64.2, 61.8, 60.7, 54.1 |
10 | 7.80—6.32(m, 17H, ArH), 4.23(t, J=6.0 Hz, 2H, OCH2CH2CH2CH2Br), 3.60(t, 2H, J=6.0 Hz, OCH2CH2CH2CH2Br), 2.22—2.17(m, 4H, OCH2CH2CH2CH2Br) | |
11 | 8.26—6.30(m, 17H, ArH), 4.33(t, J=5.2 Hz, 2H, OCH2CH2CH2CH2N), 3.85(t, 2H, J=5.2 Hz, OCH2CH2CH2CH2N), 3.47[m, 4H, N(CH2C7H15)2], 3.40(s, 3H, NCH3), 2.16—2.12(m, 4H, OCH2CH2CH2CH2N), 1.72—1.70[m, 4H, N(CH2CH2C6H13)2], 1.39—1.24[m, 20H, N(C2H4C5H10CH3)2], 0.87[t, J=6.8 Hz, 6H, N(C7H14CH3)2] | 184.6, 155.4, 154.6, 153.6, 144.0, 142.8, 136.2, 133.6, 133.1, 132.4, 132.3, 132.1, 131.9, 131.4, 131.1, 130.2, 129.3, 128.9, 128.4, 127.6, 127.5, 126.3, 126.1, 125.8, 125.6, 122.0, 104.9, 67.0, 61.6, 49.0, 31.6, 29.1, 26.4, 22.5, 14.1 |
Compd. | IC50/(μmol·L-1) | |||
---|---|---|---|---|
A375 | BGC | HepG2 | HELF | |
Emodin | 44.91 | >50 | >50 | 46 |
2a | 24.88±2.42 | >50 | >50 | >50 |
2b | 2.86±0.03 | 4.05±0.07 | 4.35±0.67 | 6.84±1.16 |
2c | 5.83±0.89 | 11.62±0.25 | 5.41±0.16 | 11.85±1.24 |
4a | 4.17±1.16 | 10.3±1.32 | 5.12±0.64 | 11.52±0.31 |
4b | 4.08±0.11 | 5.96±0.52 | 7.89±0.66 | 6.65±0.34 |
4c | 3.86±0.32 | 4.26±0.22 | 5.60±0.61 | 4.81±0.98 |
4d | 8.16±0.86 | 10.63±0.56 | 11.08±0.38 | 9.62±1.59 |
7a | 9.10±0.52 | 11.33±0.89 | ||
7b | 9.07±0.65 | 12.11±0.37 | ||
9 | >100 | >100 | ||
11 | 17.84±0.87 | |||
Paclitaxel | 11.26±0.15 | 9.26±0.14 | 10.32±0.02 | 7.14±0.09 |
Table 3 Anticancer activities(IC50) of compounds in vivo against cancer line cells and normal cell
Compd. | IC50/(μmol·L-1) | |||
---|---|---|---|---|
A375 | BGC | HepG2 | HELF | |
Emodin | 44.91 | >50 | >50 | 46 |
2a | 24.88±2.42 | >50 | >50 | >50 |
2b | 2.86±0.03 | 4.05±0.07 | 4.35±0.67 | 6.84±1.16 |
2c | 5.83±0.89 | 11.62±0.25 | 5.41±0.16 | 11.85±1.24 |
4a | 4.17±1.16 | 10.3±1.32 | 5.12±0.64 | 11.52±0.31 |
4b | 4.08±0.11 | 5.96±0.52 | 7.89±0.66 | 6.65±0.34 |
4c | 3.86±0.32 | 4.26±0.22 | 5.60±0.61 | 4.81±0.98 |
4d | 8.16±0.86 | 10.63±0.56 | 11.08±0.38 | 9.62±1.59 |
7a | 9.10±0.52 | 11.33±0.89 | ||
7b | 9.07±0.65 | 12.11±0.37 | ||
9 | >100 | >100 | ||
11 | 17.84±0.87 | |||
Paclitaxel | 11.26±0.15 | 9.26±0.14 | 10.32±0.02 | 7.14±0.09 |
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