Synthesis of Lipiophilic Cations of Anthraquinone and Their Anticancer Activities†

doi:10.7503/cjcu20141145

Abstract

Abstract:

Seven emodin quaternary ammonium salts, two aloe emodin quaternary ammonium salts, one water soluble emodin quaternary ammonium as well as a quaternary ammonium salt of α-naphtholbenzein were synthesized and the in vitro anticancer activities were tested. Emodin quaternary ammonium salts containing one long carbon chain showed very low anticancer activities, and emodin and aloe emodin quaternary ammonium salts containing two carbon chains exhibited high anticancer activities. Using hydrophilic long chains to replace lipiophilic long carbon chains made emodin quaternary ammonium salts lose anticancer activities. Quaternary ammonium salt of α-naphtholbenzein showed a moderate anticancer activity, which indicated that the introduction of lipiophilic cations to a molecule with ability to transfer electrons could increase its anticancer activity.

Key words: Emodin, Aloe emodin, Lipiophilic cation, Anticancer activity

TrendMD:

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^†[J]. Chem. J. Chinese Universities, 2015, 36(6): 1100.

Figures/Tables 9

References 21

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Compd.	Appearance	Yield(%)	m. p./℃	Elemental analysis(%, calcd.)			LC-MS, m/z	HRMS(Calcd.), m/z
Compd.	Appearance	Yield(%)	m. p./℃	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.	Appearance	Yield(%)	m. p./℃	Elemental analysis(%, calcd.)			LC-MS, m/z	HRMS(Calcd.), m/z
Compd.	Appearance	Yield(%)	m. p./℃	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

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)
Compd.	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