β-咔啉衍生物的抗肿瘤及抗菌活性

doi:10.7503/cjcu20170636

摘要/Abstract

摘要：

以L-色氨酸为原料合成了72个不同取代基的β-咔啉化合物, 其中31个新化合物, 包括12对手性化合物. 采用噻唑蓝(MTT)法对5种肿瘤细胞株及5种菌株进行了体外抗肿瘤活性、抗菌活性的筛选及构效关系研究. 生物活性测试结果表明, 部分目标化合物具有一定的抗肿瘤活性(化合物3b对A549细胞的IC₅₀=3.17 μmol/L), 且具有不同程度的抑菌活性(化合物5h对鳗弧菌的MIC=0.78 μmol/L).

关键词: β-咔啉化合物, 抗菌活性, 抗肿瘤活性, 手性化合物

Abstract:

A series of β-carbolines possessing different substituents at C1, C3 and N9 positions derived from L-tryptophan was used in anti-tumour and antimicrobial activity study. Compound 3b exhibited anti-tumour activity against tumour cell line A459 with a IC₅₀ value of 3.17 μmol/L in vitro by methyl thiazolyl tetrazolium(MTT) assay while the positive control group(cis-platin, DDP) was 1.45 μmol/L. Other eleven compounds showed relatively weak activities against the five cell-lines. Compound 5h exhibited activitiy against vibrio anguillarum with a MIC value of 0.78 μmol/L while the positive control group(ciprofloxacin) was 1.25 μmol/L. Other fourteen compounds showed relatively weak activities against five spices of bacteria. By the study of structural-activity relationship, optimizing structures is possible and necessary in the future to screen potential compounds for medicinal study.

Key words: β-Carboline, Antimicrobial activity, Anti-tumor activity, Chiral compound

中图分类号:

O626

TrendMD:

刘莉, 马洋洋, 王宽, 贾云静, 李婉, 朱华结. β-咔啉衍生物的抗肿瘤及抗菌活性. 高等学校化学学报, 2018, 39(4): 674.

LIU Li, MA Yangyang, WANG Kuan, JIA Yunjing, LI Wan, ZHU Huajie. Anti-tumor and Antimicrobial Activities of β-Carbolines^†. Chem. J. Chinese Universities, 2018, 39(4): 674.

图/表 5

参考文献 30

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Compd.	Appearance	Yield(%)	Elemental analysis(%, cacld. )
Compd.	Appearance	Yield(%)	C	H	N
5b	Yellow oil	86	70.73(70.70)	4.69(4.68)	8.72(8.68)
5c	Yellow oil	85	70.73(70.70)	4.69(4.68)	8.72(8.68)
5d	Yellow oil	93	79.41(79.44)	6.03(6.00)	9.27(9.26)
5f	Yellow oil	89	74.54(74.50)	4.91(4.94)	9.13(9.14)
5j	Yellow oil	90	75.41(75.45)	5.73(5.70)	8.83(8.80)
5k	Yellow oil	85	68.49(68.46)	4.53(4.54)	12.63(12.61)
5l	Yellow oil	87	77.49(77.52)	7.54(7.53)	9.55(9.52)
7a	Yellow oil	89	80.67(80.71)	5.83(5.85)	8.59(8.56)
7b	Yellow oil	73	73.05(73.02)	5.05(5.01)	7.73(7.74)
7c	Yellow oil	63	73.05(73.02)	5.05(5.01)	7.73(7.74)
7d	Yellow oil	55	80.89(80.91)	6.17(6.20)	8.23(8.20)
7e	Yellow oil	48	76.47(76.50)	5.27(5.25)	8.13(8.11)
7f	Yellow oil	61	76.49(76.50)	5.29(5.25)	8.11(8.11)
7g	Yellow oil	56	82.77(82.73)	5.64(5.61)	7.39(7.42)
7h	Yellow oil	77	82.75(82.73)	5.63(5.61)	7.38(7.42)
7i	Yellow oil	69	77.27(77.29)	5.97(5.92)	7.83(7.84)
7j	Yellow oil	77	77.26(77.29)	5.95(5.92)	7.81(7.84)
7k	Yellow oil	79	70.93(70.96)	4.85(4.87)	11.24(11.28)
7l	Yellow oil	86	79.21(79.24)	7.58(7.56)	8.39(8.40)

Compd.	Appearance	Yield(%)	Elemental analysis(%, cacld. )
Compd.	Appearance	Yield(%)	C	H	N
5b	Yellow oil	86	70.73(70.70)	4.69(4.68)	8.72(8.68)
5c	Yellow oil	85	70.73(70.70)	4.69(4.68)	8.72(8.68)
5d	Yellow oil	93	79.41(79.44)	6.03(6.00)	9.27(9.26)
5f	Yellow oil	89	74.54(74.50)	4.91(4.94)	9.13(9.14)
5j	Yellow oil	90	75.41(75.45)	5.73(5.70)	8.83(8.80)
5k	Yellow oil	85	68.49(68.46)	4.53(4.54)	12.63(12.61)
5l	Yellow oil	87	77.49(77.52)	7.54(7.53)	9.55(9.52)
7a	Yellow oil	89	80.67(80.71)	5.83(5.85)	8.59(8.56)
7b	Yellow oil	73	73.05(73.02)	5.05(5.01)	7.73(7.74)
7c	Yellow oil	63	73.05(73.02)	5.05(5.01)	7.73(7.74)
7d	Yellow oil	55	80.89(80.91)	6.17(6.20)	8.23(8.20)
7e	Yellow oil	48	76.47(76.50)	5.27(5.25)	8.13(8.11)
7f	Yellow oil	61	76.49(76.50)	5.29(5.25)	8.11(8.11)
7g	Yellow oil	56	82.77(82.73)	5.64(5.61)	7.39(7.42)
7h	Yellow oil	77	82.75(82.73)	5.63(5.61)	7.38(7.42)
7i	Yellow oil	69	77.27(77.29)	5.97(5.92)	7.83(7.84)
7j	Yellow oil	77	77.26(77.29)	5.95(5.92)	7.81(7.84)
7k	Yellow oil	79	70.93(70.96)	4.85(4.87)	11.24(11.28)
7l	Yellow oil	86	79.21(79.24)	7.58(7.56)	8.39(8.40)

Compd.	¹H NMR(CDCl₃, 600 MHz), δ	¹³C NMR(CDCl₃, 150 MHz), δ
5b	8.17(d, J=7.8 Hz, 1H), 7.95(s, 1H), 7.64-7.59(m, 3H), 7.52(d, J=8.4 Hz, 2H), 7.43(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 4.96(s, 2H), 3.49(s, 3H)	145.12(s), 143.90(s), 137.50(s), 136.75(s), 134.54(s), 132.11(s), 131.65(s), 131.00(s), 128.42(s), 126.16(s), 122.12(s), 121.54(s), 118.68(s), 113.44(s), 109.74(s), 60.18(s), 32.27(s)
5c	8.09(d, J=7.8 Hz, 1H), 7.89(s, 1H), 7.60(s, 1H), 7.55(t, J=7.7 Hz, 1H), 7.46(t, J=7.4 Hz, 1H), 7.40(d, J=6.7 Hz, 2H), 7.36(d, J=8.3 Hz, 1H), 7.25(t, J=7.4 Hz, 1H), 4.89(s, 2H), 3.42(s, 3H)	147.93, 143.64, 141.35, 141.09, 134.56, 134.24, 131.62, 129.88, 129.43, 128.89, 128.63, 127.93, 121.66, 121.03, 120.07, 110.61, 109.87, 64.77, 33.15
5d	8.15(d, J=7.8 Hz, 1H), 7.90(s, 1H), 7.60(t, J=7.6 Hz, 1H), 7.53(d, J=7.7 Hz, 2H), 7.41(d, J=8.2 Hz, 1H), 7.33(d, J=7.6 Hz, 2H), 7.29(t, J=7.5 Hz, 1H), 4.94(s, 2H), 3.46(d, J=12.7 Hz, 3H), 2.46(s, 3H)	147.60(s), 143.56(s), 142.98(s), 138.39(s), 136.69(s), 134.61(s), 131.20(s), 129.61(s), 128.87(s), 128.61(s), 121.60(s), 121.09(s), 119.81(s), 109.97(s), 109.81(s), 64.69(s), 32.95(s), 21.41(s)
5f	8.15(d, J=7.8 Hz, 1H), 7.93(s, 1H), 7.61(dd, J=10.6, 5.4 Hz, 3H), 7.41(d, J=8.3 Hz, 1H), 7.31(t, J=7.5 Hz, 1H), 7.21(t, J=8.5 Hz, 2H), 4.95(s, 2H), 3.46(s, 3H)	163.82(s), 162.18(s), 147.93(s), 143.61(s), 141.72(s), 135.67(s), 134.60(s), 131.47(d, J=8.0 Hz), 128.80(s), 121.64(s), 121.06(s), 120.00(s), 115.31(s), 115.22(d, J=21.4 Hz), 110.39(s), 109.83(s), 64.78(s), 32.99(s)
5j	8.14(t, J=8.7 Hz, 1H), 7.93(s, 1H), 7.60(t, J=7.7 Hz, 1H), 7.46-7.37(m, 2H), 7.34-7.28(m, 1H), 7.19(d, J=7.3 Hz, 2H), 7.07-7.02(m, 1H), 4.99-4.92(m, 2H), 3.85(d, J=21.5 Hz, 3H), 3.47(s, 3H)	159.44(s), 147.70(s), 143.54(s), 142.69(s), 140.90(s), 134.48(s), 131.24(s), 129.21(s), 128.67(s), 122.26(s), 121.60(s), 121.06(s), 119.86(s), 115.05(s), 114.46(s), 110.31(s), 109.80(s), 64.82(s), 55.41(s), 32.81(s)
5k	8.41(d, J=8.6 Hz, 2H), 8.18(d, J=7.8 Hz, 1H), 8.00(d, J=10.9 Hz, 1H), 7.87(d, J=8.5 Hz, 2H), 7.65(t, J=7.6 Hz, 1H), 7.45(d, J=8.3 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 4.98(s, 2H), 3.49(d, J=9.5 Hz, 3H)	147.24(s), 146.78(s), 143.30(s), 137.93(s), 133.40(s), 131.96(s), 130.03(s), 129.03(s), 122.54(s) 121.06(s), 119.92(s), 119.73(s), 111.00(s), 109.13(s), 62.96(s), 32.47(s)
5l	8.08(d, J=7.8 Hz, 1H), 7.68(s, 1H), 7.59(t, J=7.6 Hz, 1H), 7.44(d, J=8.3 Hz, 1H), 7.24(s, 1H), 4.88(s, 2H), 4.11(d, J=11.2 Hz, 3H), 3.55(t, J=11.2 Hz, 1H), 1.98(dd, J=38.0, 10.3 Hz, 6H), 1.55-1.38(m, 4H)	148.64(s), 146.41(s), 143.04(s), 134.09(s), 130.71(s), 128.28(s), 121.31(s), 121.13(s), 119.47(s), 109.44(s), 108.31(s), 63.91(s), 32.93(s), 32.65(s), 29.69(s), 26.76(s), 26.15(s)
7a	8.13(d, J=1.8 Hz, 1H), 7.90(s, 1H), 7.64(d, J=6.6 Hz, 2H), 7.60-7.41(m, 5H), 7.33(d, J=8.7 Hz, 1H), 5.92(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.20-5.10(m, 2H), 5.03(dd, J=7.3, 4.9 Hz, 1H), 3.45(s, 3H), 2.79-2.73(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H)	150.51, 142.87, 141.86, 139.29, 134.90, 134.78, 130.22, 129.76, 128.80, 128.65, 128.20, 125.41, 122.22, 121.23, 117.74, 110.93, 109.84, 77.23, 77.02, 76.81, 72.51, 43.53, 33.12
7b	8.10(d, J=7.8 Hz, 1H), 7.89(s, 1H), 7.61-7.52(m, 3H), 7.45(t, J=7.2 Hz, 2H), 7.35(t, J=6.9 Hz, 1H), 7.25(t, J=7.5 Hz, 1H), 5.86(ddt, J=17.2, 10.2, 7.1 Hz, 1H), 5.07(dd, J=27.4, 13.6 Hz, 2H), 4.98-4.94(m, 1H), 3.41(d, J=16.5 Hz, 3H), 2.73-2.67(m, 1H), 2.55(dt, J=14.4, 7.3 Hz, 1H)	149.34, 142.69, 139.92, 133.80, 133.63, 133.55, 130.54, 130.12, 127.82, 127.39, 120.63, 120.13, 119.02, 116.69, 109.01, 108.85, 71.46, 42.55, 32.18
7c	8.18(d, J=7.8 Hz, 1H), 7.99(s, 1H), 7.67(s, 1H), 7.63(t, J=7.7 Hz, 1H), 7.55(t, J=7.1 Hz, 1H), 7.50-7.45(m, 2H), 7.43(d, J=8.3 Hz, 1H), 7.33(t, J=7.5 Hz, 1H), 5.93(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.10(m, 2H), 5.05(dd, J=7.1, 4.9 Hz, 1H), 3.50(s, 3H), 2.80-2.75(m, 1H), 2.63(dt, J=14.3, 7.3 Hz, 1H)	143.76, 140.57, 134.75, 134.51, 134.20, 131.69, 129.95, 129.43, 128.97, 128.67, 128.03, 121.70, 121.08, 120.12, 117.80, 110.29, 109.89, 72.51, 53.41, 43.51, 33.17
7d	8.17(d, J=7.8 Hz, 1H), 7.93(s, 1H), 7.61(t, J=7.7 Hz, 1H), 7.55(d, J=7.8 Hz, 2H), 7.42(d, J=8.3 Hz, 1H), 7.35-7.28(m, 3H), 5.94(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.13(dd, J=29.9, 13.6 Hz, 2H), 5.04-4.99(m, 1H), 3.49(s, 3H), 2.79-2.74(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H), 2.48(s, 3H)	150.04, 143.66, 138.38, 135.00, 134.59, 131.21, 129.69, 128.83, 128.58, 121.58, 121.20, 119.80, 117.50, 109.81, 109.53, 72.43, 43.61, 33.00, 21.39
Compd.	¹H NMR(CDCl₃, 600 MHz), δ	¹³C NMR(CDCl₃, 150 MHz), δ
7e	8.17(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.63(ddd, J=15.0, 6.8, 1.4 Hz, 3H), 7.42(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 7.23(t, J=8.6 Hz, 2H), 5.93(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.09(m, 2H), 5.03(dd, J=7.4, 4.8 Hz, 1H), 3.48(s, 3H), 2.80-2.73(m, 1H), 2.62(dt, J=14.4, 7.4 Hz, 1H)	162.82, 161.18, 149.29, 142.69, 140.24, 134.71, 133.84, 133.60, 130.54, 130.49, 127.76, 120.62, 120.16, 118.97, 116.65, 114.24, 114.10, 108.88, 108.83, 71.51, 42.55, 32.04
7f	8.17(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.67-7.59(m, 3H), 7.42(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 7.23(t, J=8.6 Hz, 2H), 5.93(ddt, J=17.2, 10.1, 7.0 Hz, 1H), 5.14(dd, J=27.9, 13.7 Hz, 2H), 5.03(dd, J=7.3, 4.8 Hz, 1H), 3.48(s, 3H), 2.80-2.73(m, 1H), 2.62(dt, J=14.5, 7.3 Hz, 1H)	163.84, 162.19, 150.29, 143.70, 141.24, 134.85, 134.61, 131.55, 131.50, 131.46, 128.78, 121.64, 121.17, 119.99, 117.67, 115.25, 115.11, 109.89, 109.84, 72.52, 43.56, 33.05
7g	8.26(d, J=8.0 Hz, 1H), 8.10(d, J=5.0 Hz, 1H), 8.04(d, J=8.9 Hz, 1H), 7.99(d, J=8.2 Hz, 1H), 7.70-7.64(m, 2H), 7.62(t, J=7.7 Hz, 1H), 7.56-7.51(m, 1H), 7.43(t, J=8.2 Hz, 1H), 7.38(dd, J=13.2, 5.9 Hz, 1H), 7.34(dd, J=7.7, 5.5 Hz, 2H), 6.02-5.91(m, 1H), 5.22-5.08(m, 3H), 3.10(s, 3H), 2.83(ddd, J=19.9, 13.8, 5.8 Hz, 1H), 2.67(td, J=14.0, 7.0 Hz, 1H)	149.19, 142.14, 139.97, 134.40, 133.88, 133.81, 132.44, 131.79, 129.63, 127.98, 127.64, 127.34, 126.95, 125.63, 125.16, 124.94, 124.17, 120.67, 120.00, 118.77, 116.67, 109.11, 108.60, 71.64, 42.67, 30.32
7h	8.23(d, J=8.0 Hz, 1H), 8.07(d, J=4.6 Hz, 1H), 8.03-7.99(m, 1H), 7.96(d, J=8.2 Hz, 1H), 7.66-7.62(m, 2H), 7.59(t, J=7.7 Hz, 1H), 7.53-7.48(m, 1H), 7.41(t, J=8.1 Hz, 1H), 7.35(dd, J=13.4, 5.9 Hz, 1H), 7.34-7.29(m, 2H), 5.98-5.89(m, 1H), 5.12(ddd, J=21.6, 14.3, 9.2 Hz, 3H), 3.07(s, 3H), 2.84-2.76(m, 1H), 2.64(dq, J=13.8, 6.9 Hz, 1H)	150.28, 143.12, 141.04, 136.96, 135.43, 134.85, 133.47, 132.82, 130.58, 128.96, 128.61, 128.35, 127.88, 126.66, 126.16, 125.98, 125.19, 121.67, 121.04, 119.76, 117.66, 110.08, 109.61, 72.78, 43.74, 31.35
7i	8.17(d, J=7.8 Hz, 1H), 7.92(s, 1H), 7.61(dd, J=19.8, 10.6 Hz, 3H), 7.42(d, J=8.3 Hz, 1H), 7.30(t, J=7.5 Hz, 1H), 7.06(d, J=8.5 Hz, 2H), 5.94(ddt, J=17.1, 10.1, 7.0 Hz, 1H), 5.14(dd, J=30.2, 13.6 Hz, 2H), 5.03(dd, J=7.3, 4.8 Hz, 1H), 3.91(s, 3H), 3.51(s, 3H), 2.80-2.74(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H)	159.95, 150.06, 143.72, 142.20, 134.98, 134.63, 131.27, 131.03, 128.62, 121.60, 121.22, 119.83, 117.53, 113.62, 109.84, 109.47, 72.44, 55.42, 43.56, 33.01
7j	8.18(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.66-7.58(m, 1H), 7.46-7.39(m, 2H), 7.30(dd, J=18.7, 11.3 Hz, 1H), 7.21(dd, J=8.0, 4.8 Hz, 2H), 7.05(dd, J=8.3, 2.1 Hz, 1H), 5.94(ddt, J=17.1, 10.1, 7.0 Hz, 1H), 5.14(dd, J=29.4, 13.7 Hz, 2H), 5.04(dd, J=7.4, 4.8 Hz, 1H), 3.89(s, 3H), 3.49(s, 3H), 2.81-2.74(m, 1H), 2.62(dt, J=14.4, 7.4 Hz, 1H)	159.41, 150.07, 143.64, 142.15, 134.95, 134.48, 131.26, 129.16, 128.68, 122.35, 121.61, 121.14, 119.87, 117.61, 115.21, 114.36, 109.84, 109.82, 72.52, 55.42, 43.59, 32.89, 29.70
7k	8.41(d, J=8.6 Hz, 2H), 8.19(d, J=7.8 Hz, 1H), 8.03(s, 1H), 7.89-7.86(m, 2H), 7.67-7.63(m, 1H), 7.45(d, J=8.3 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 5.92(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.11(m, 2H), 5.05(dd, J=7.3, 4.8 Hz, 1H), 3.50(s, 3H), 2.81-2.75(m, 1H), 2.63(dt, J=14.4, 7.3 Hz, 1H)	167.71, 150.86, 147.83, 146.02, 143.85, 139.34, 134.73, 134.58, 132.12, 130.79, 129.22, 123.42, 121.77, 121.13, 120.42, 117.95, 110.87, 109.98, 72.53, 43.50, 33.57
7l	8.03(d, J=7.7 Hz, 1H), 7.64(s, 1H), 7.52(t, J=7.6 Hz, 1H), 7.37(d, J=8.3 Hz, 1H), 7.22-7.16(m, 2H), 5.83(ddt, J=17.1, 10.2, 7.0 Hz, 1H), 5.08-4.98(m, 2H), 4.90-4.85(m, 1H), 3.51-3.42(m, 1H), 2.67-2.59(m, 1H), 2.50(dt, J=13.8, 6.8 Hz, 1H), 1.99-1.83(m, 7H), 1.76(d, J=12.7 Hz, 1H), 1.46-1.41(m, 2H), 1.35-1.30(m, 1H)	147.95, 147.27, 141.97, 134.02, 132.95, 129.55, 127.21, 120.29, 120.20, 118.44, 116.12, 108.41, 107.31, 70.98, 42.73, 41.04, 31.93, 31.88, 31.61, 28.68, 25.72, 25.14

Compd.	¹H NMR(CDCl₃, 600 MHz), δ	¹³C NMR(CDCl₃, 150 MHz), δ
5b	8.17(d, J=7.8 Hz, 1H), 7.95(s, 1H), 7.64-7.59(m, 3H), 7.52(d, J=8.4 Hz, 2H), 7.43(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 4.96(s, 2H), 3.49(s, 3H)	145.12(s), 143.90(s), 137.50(s), 136.75(s), 134.54(s), 132.11(s), 131.65(s), 131.00(s), 128.42(s), 126.16(s), 122.12(s), 121.54(s), 118.68(s), 113.44(s), 109.74(s), 60.18(s), 32.27(s)
5c	8.09(d, J=7.8 Hz, 1H), 7.89(s, 1H), 7.60(s, 1H), 7.55(t, J=7.7 Hz, 1H), 7.46(t, J=7.4 Hz, 1H), 7.40(d, J=6.7 Hz, 2H), 7.36(d, J=8.3 Hz, 1H), 7.25(t, J=7.4 Hz, 1H), 4.89(s, 2H), 3.42(s, 3H)	147.93, 143.64, 141.35, 141.09, 134.56, 134.24, 131.62, 129.88, 129.43, 128.89, 128.63, 127.93, 121.66, 121.03, 120.07, 110.61, 109.87, 64.77, 33.15
5d	8.15(d, J=7.8 Hz, 1H), 7.90(s, 1H), 7.60(t, J=7.6 Hz, 1H), 7.53(d, J=7.7 Hz, 2H), 7.41(d, J=8.2 Hz, 1H), 7.33(d, J=7.6 Hz, 2H), 7.29(t, J=7.5 Hz, 1H), 4.94(s, 2H), 3.46(d, J=12.7 Hz, 3H), 2.46(s, 3H)	147.60(s), 143.56(s), 142.98(s), 138.39(s), 136.69(s), 134.61(s), 131.20(s), 129.61(s), 128.87(s), 128.61(s), 121.60(s), 121.09(s), 119.81(s), 109.97(s), 109.81(s), 64.69(s), 32.95(s), 21.41(s)
5f	8.15(d, J=7.8 Hz, 1H), 7.93(s, 1H), 7.61(dd, J=10.6, 5.4 Hz, 3H), 7.41(d, J=8.3 Hz, 1H), 7.31(t, J=7.5 Hz, 1H), 7.21(t, J=8.5 Hz, 2H), 4.95(s, 2H), 3.46(s, 3H)	163.82(s), 162.18(s), 147.93(s), 143.61(s), 141.72(s), 135.67(s), 134.60(s), 131.47(d, J=8.0 Hz), 128.80(s), 121.64(s), 121.06(s), 120.00(s), 115.31(s), 115.22(d, J=21.4 Hz), 110.39(s), 109.83(s), 64.78(s), 32.99(s)
5j	8.14(t, J=8.7 Hz, 1H), 7.93(s, 1H), 7.60(t, J=7.7 Hz, 1H), 7.46-7.37(m, 2H), 7.34-7.28(m, 1H), 7.19(d, J=7.3 Hz, 2H), 7.07-7.02(m, 1H), 4.99-4.92(m, 2H), 3.85(d, J=21.5 Hz, 3H), 3.47(s, 3H)	159.44(s), 147.70(s), 143.54(s), 142.69(s), 140.90(s), 134.48(s), 131.24(s), 129.21(s), 128.67(s), 122.26(s), 121.60(s), 121.06(s), 119.86(s), 115.05(s), 114.46(s), 110.31(s), 109.80(s), 64.82(s), 55.41(s), 32.81(s)
5k	8.41(d, J=8.6 Hz, 2H), 8.18(d, J=7.8 Hz, 1H), 8.00(d, J=10.9 Hz, 1H), 7.87(d, J=8.5 Hz, 2H), 7.65(t, J=7.6 Hz, 1H), 7.45(d, J=8.3 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 4.98(s, 2H), 3.49(d, J=9.5 Hz, 3H)	147.24(s), 146.78(s), 143.30(s), 137.93(s), 133.40(s), 131.96(s), 130.03(s), 129.03(s), 122.54(s) 121.06(s), 119.92(s), 119.73(s), 111.00(s), 109.13(s), 62.96(s), 32.47(s)
5l	8.08(d, J=7.8 Hz, 1H), 7.68(s, 1H), 7.59(t, J=7.6 Hz, 1H), 7.44(d, J=8.3 Hz, 1H), 7.24(s, 1H), 4.88(s, 2H), 4.11(d, J=11.2 Hz, 3H), 3.55(t, J=11.2 Hz, 1H), 1.98(dd, J=38.0, 10.3 Hz, 6H), 1.55-1.38(m, 4H)	148.64(s), 146.41(s), 143.04(s), 134.09(s), 130.71(s), 128.28(s), 121.31(s), 121.13(s), 119.47(s), 109.44(s), 108.31(s), 63.91(s), 32.93(s), 32.65(s), 29.69(s), 26.76(s), 26.15(s)
7a	8.13(d, J=1.8 Hz, 1H), 7.90(s, 1H), 7.64(d, J=6.6 Hz, 2H), 7.60-7.41(m, 5H), 7.33(d, J=8.7 Hz, 1H), 5.92(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.20-5.10(m, 2H), 5.03(dd, J=7.3, 4.9 Hz, 1H), 3.45(s, 3H), 2.79-2.73(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H)	150.51, 142.87, 141.86, 139.29, 134.90, 134.78, 130.22, 129.76, 128.80, 128.65, 128.20, 125.41, 122.22, 121.23, 117.74, 110.93, 109.84, 77.23, 77.02, 76.81, 72.51, 43.53, 33.12
7b	8.10(d, J=7.8 Hz, 1H), 7.89(s, 1H), 7.61-7.52(m, 3H), 7.45(t, J=7.2 Hz, 2H), 7.35(t, J=6.9 Hz, 1H), 7.25(t, J=7.5 Hz, 1H), 5.86(ddt, J=17.2, 10.2, 7.1 Hz, 1H), 5.07(dd, J=27.4, 13.6 Hz, 2H), 4.98-4.94(m, 1H), 3.41(d, J=16.5 Hz, 3H), 2.73-2.67(m, 1H), 2.55(dt, J=14.4, 7.3 Hz, 1H)	149.34, 142.69, 139.92, 133.80, 133.63, 133.55, 130.54, 130.12, 127.82, 127.39, 120.63, 120.13, 119.02, 116.69, 109.01, 108.85, 71.46, 42.55, 32.18
7c	8.18(d, J=7.8 Hz, 1H), 7.99(s, 1H), 7.67(s, 1H), 7.63(t, J=7.7 Hz, 1H), 7.55(t, J=7.1 Hz, 1H), 7.50-7.45(m, 2H), 7.43(d, J=8.3 Hz, 1H), 7.33(t, J=7.5 Hz, 1H), 5.93(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.10(m, 2H), 5.05(dd, J=7.1, 4.9 Hz, 1H), 3.50(s, 3H), 2.80-2.75(m, 1H), 2.63(dt, J=14.3, 7.3 Hz, 1H)	143.76, 140.57, 134.75, 134.51, 134.20, 131.69, 129.95, 129.43, 128.97, 128.67, 128.03, 121.70, 121.08, 120.12, 117.80, 110.29, 109.89, 72.51, 53.41, 43.51, 33.17
7d	8.17(d, J=7.8 Hz, 1H), 7.93(s, 1H), 7.61(t, J=7.7 Hz, 1H), 7.55(d, J=7.8 Hz, 2H), 7.42(d, J=8.3 Hz, 1H), 7.35-7.28(m, 3H), 5.94(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.13(dd, J=29.9, 13.6 Hz, 2H), 5.04-4.99(m, 1H), 3.49(s, 3H), 2.79-2.74(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H), 2.48(s, 3H)	150.04, 143.66, 138.38, 135.00, 134.59, 131.21, 129.69, 128.83, 128.58, 121.58, 121.20, 119.80, 117.50, 109.81, 109.53, 72.43, 43.61, 33.00, 21.39
Compd.	¹H NMR(CDCl₃, 600 MHz), δ	¹³C NMR(CDCl₃, 150 MHz), δ
7e	8.17(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.63(ddd, J=15.0, 6.8, 1.4 Hz, 3H), 7.42(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 7.23(t, J=8.6 Hz, 2H), 5.93(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.09(m, 2H), 5.03(dd, J=7.4, 4.8 Hz, 1H), 3.48(s, 3H), 2.80-2.73(m, 1H), 2.62(dt, J=14.4, 7.4 Hz, 1H)	162.82, 161.18, 149.29, 142.69, 140.24, 134.71, 133.84, 133.60, 130.54, 130.49, 127.76, 120.62, 120.16, 118.97, 116.65, 114.24, 114.10, 108.88, 108.83, 71.51, 42.55, 32.04
7f	8.17(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.67-7.59(m, 3H), 7.42(d, J=8.3 Hz, 1H), 7.32(t, J=7.5 Hz, 1H), 7.23(t, J=8.6 Hz, 2H), 5.93(ddt, J=17.2, 10.1, 7.0 Hz, 1H), 5.14(dd, J=27.9, 13.7 Hz, 2H), 5.03(dd, J=7.3, 4.8 Hz, 1H), 3.48(s, 3H), 2.80-2.73(m, 1H), 2.62(dt, J=14.5, 7.3 Hz, 1H)	163.84, 162.19, 150.29, 143.70, 141.24, 134.85, 134.61, 131.55, 131.50, 131.46, 128.78, 121.64, 121.17, 119.99, 117.67, 115.25, 115.11, 109.89, 109.84, 72.52, 43.56, 33.05
7g	8.26(d, J=8.0 Hz, 1H), 8.10(d, J=5.0 Hz, 1H), 8.04(d, J=8.9 Hz, 1H), 7.99(d, J=8.2 Hz, 1H), 7.70-7.64(m, 2H), 7.62(t, J=7.7 Hz, 1H), 7.56-7.51(m, 1H), 7.43(t, J=8.2 Hz, 1H), 7.38(dd, J=13.2, 5.9 Hz, 1H), 7.34(dd, J=7.7, 5.5 Hz, 2H), 6.02-5.91(m, 1H), 5.22-5.08(m, 3H), 3.10(s, 3H), 2.83(ddd, J=19.9, 13.8, 5.8 Hz, 1H), 2.67(td, J=14.0, 7.0 Hz, 1H)	149.19, 142.14, 139.97, 134.40, 133.88, 133.81, 132.44, 131.79, 129.63, 127.98, 127.64, 127.34, 126.95, 125.63, 125.16, 124.94, 124.17, 120.67, 120.00, 118.77, 116.67, 109.11, 108.60, 71.64, 42.67, 30.32
7h	8.23(d, J=8.0 Hz, 1H), 8.07(d, J=4.6 Hz, 1H), 8.03-7.99(m, 1H), 7.96(d, J=8.2 Hz, 1H), 7.66-7.62(m, 2H), 7.59(t, J=7.7 Hz, 1H), 7.53-7.48(m, 1H), 7.41(t, J=8.1 Hz, 1H), 7.35(dd, J=13.4, 5.9 Hz, 1H), 7.34-7.29(m, 2H), 5.98-5.89(m, 1H), 5.12(ddd, J=21.6, 14.3, 9.2 Hz, 3H), 3.07(s, 3H), 2.84-2.76(m, 1H), 2.64(dq, J=13.8, 6.9 Hz, 1H)	150.28, 143.12, 141.04, 136.96, 135.43, 134.85, 133.47, 132.82, 130.58, 128.96, 128.61, 128.35, 127.88, 126.66, 126.16, 125.98, 125.19, 121.67, 121.04, 119.76, 117.66, 110.08, 109.61, 72.78, 43.74, 31.35
7i	8.17(d, J=7.8 Hz, 1H), 7.92(s, 1H), 7.61(dd, J=19.8, 10.6 Hz, 3H), 7.42(d, J=8.3 Hz, 1H), 7.30(t, J=7.5 Hz, 1H), 7.06(d, J=8.5 Hz, 2H), 5.94(ddt, J=17.1, 10.1, 7.0 Hz, 1H), 5.14(dd, J=30.2, 13.6 Hz, 2H), 5.03(dd, J=7.3, 4.8 Hz, 1H), 3.91(s, 3H), 3.51(s, 3H), 2.80-2.74(m, 1H), 2.62(dt, J=14.4, 7.3 Hz, 1H)	159.95, 150.06, 143.72, 142.20, 134.98, 134.63, 131.27, 131.03, 128.62, 121.60, 121.22, 119.83, 117.53, 113.62, 109.84, 109.47, 72.44, 55.42, 43.56, 33.01
7j	8.18(d, J=7.8 Hz, 1H), 7.96(s, 1H), 7.66-7.58(m, 1H), 7.46-7.39(m, 2H), 7.30(dd, J=18.7, 11.3 Hz, 1H), 7.21(dd, J=8.0, 4.8 Hz, 2H), 7.05(dd, J=8.3, 2.1 Hz, 1H), 5.94(ddt, J=17.1, 10.1, 7.0 Hz, 1H), 5.14(dd, J=29.4, 13.7 Hz, 2H), 5.04(dd, J=7.4, 4.8 Hz, 1H), 3.89(s, 3H), 3.49(s, 3H), 2.81-2.74(m, 1H), 2.62(dt, J=14.4, 7.4 Hz, 1H)	159.41, 150.07, 143.64, 142.15, 134.95, 134.48, 131.26, 129.16, 128.68, 122.35, 121.61, 121.14, 119.87, 117.61, 115.21, 114.36, 109.84, 109.82, 72.52, 55.42, 43.59, 32.89, 29.70
7k	8.41(d, J=8.6 Hz, 2H), 8.19(d, J=7.8 Hz, 1H), 8.03(s, 1H), 7.89-7.86(m, 2H), 7.67-7.63(m, 1H), 7.45(d, J=8.3 Hz, 1H), 7.35(t, J=7.5 Hz, 1H), 5.92(ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.19-5.11(m, 2H), 5.05(dd, J=7.3, 4.8 Hz, 1H), 3.50(s, 3H), 2.81-2.75(m, 1H), 2.63(dt, J=14.4, 7.3 Hz, 1H)	167.71, 150.86, 147.83, 146.02, 143.85, 139.34, 134.73, 134.58, 132.12, 130.79, 129.22, 123.42, 121.77, 121.13, 120.42, 117.95, 110.87, 109.98, 72.53, 43.50, 33.57
7l	8.03(d, J=7.7 Hz, 1H), 7.64(s, 1H), 7.52(t, J=7.6 Hz, 1H), 7.37(d, J=8.3 Hz, 1H), 7.22-7.16(m, 2H), 5.83(ddt, J=17.1, 10.2, 7.0 Hz, 1H), 5.08-4.98(m, 2H), 4.90-4.85(m, 1H), 3.51-3.42(m, 1H), 2.67-2.59(m, 1H), 2.50(dt, J=13.8, 6.8 Hz, 1H), 1.99-1.83(m, 7H), 1.76(d, J=12.7 Hz, 1H), 1.46-1.41(m, 2H), 1.35-1.30(m, 1H)	147.95, 147.27, 141.97, 134.02, 132.95, 129.55, 127.21, 120.29, 120.20, 118.44, 116.12, 108.41, 107.31, 70.98, 42.73, 41.04, 31.93, 31.88, 31.61, 28.68, 25.72, 25.14

Compd.	IC₅₀/(μmol·L^-1)
Compd.	HELA	MGC-803	MCF-7	A549	SMMC-7721
3a	5.24±0.97	-	-	22.89±1.26	-
3b	-	-	-	3.17±1.11	-
3d	-	-	11.06±1.03	-	-
3f	11.73±0.78	25.88±2.92	35.19±0.99	9.92±2.11	-
3g	26.21±0.98	-	-	-	-
3h	33.47±1.27	-	-	-	-
3l	29.30±0.92	-	-	-	-
4c	-	-	-	34.95±1.48	-
4d	25.23±0.91	-	-	-	-
5f	4.47±0.87	5.93±0.71	13.43±1.23	8.77±1.49	9.73±2.69
(R,S)-7g	39.01±0.97	-	-	-	-
(R)-7h	29.18±0.89	-	-	-	-
cis-platin	5.98±0.26	10.06±0.54	5.486±0.74	1.45±0.59	11.07±1.26