Anti-tumor and Antimicrobial Activities of β-Carbolines†

doi:10.7503/cjcu20170636

Abstract

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

CLC Number:

O626

TrendMD:

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

Figures/Tables 5

References 30

[1]	Ma Y., Wink M., Phytother. Res., 2010, 24, 146-149
[2]	Bai B., Li X. Y., Liu L., Li Y., Zhu H. J., Bioorg. Med. Chem. Lett., 2014, 24, 96-98
[3]	Guo L., Cao R. H., Fan W. X., Gan Z. Y., Ma Q., Chem. J. Chinese Universities, 2016, 37(6), 1093-1099
	(郭亮, 曹日晖, 范文玺, 甘紫云, 马芹. 高等学校化学学报, 2016, 37(6), 1093-1099)
[4]	Guan H. J., Chen H. S., Peng W. L., Ma Y., Cao R. H., Liu X. D., Xu A. L., Eur. J. Med., 2006, 41, 1167-1179
[5]	Trujillo J. I., Meyers M. J., Anderson D. R., Hegde S., Mahoney M. W., Vernier W. F., Buchler I. P., Wu K., Yang S., Hartmann S. J., Reitz D. B., Bioorg. Med. Chem. Lett., 2007, 17, 4657-4663
[6]	Gregory D. C., Natalia P. U., Debasis P., Ji F. L., Xiang J. L., Ken A., Soumya S. R., Jun X., Marcie A. G., Ross L. S., Jonathan M. G. H., Bioorg. Med. Chem. Lett., 2012, 22, 2015-2019
[7]	Herraiz T., Galisteo J., J. Agr. Food. Chem., 2002, 50, 4690-4695
[8]	Schott Y., Decker M., Rommelspacher H., Lehmann J., Bioorg. Med. Chem. Lett., 2006, 16, 5840-5843
[9]	Patel K., Gadewar M., Tripathi R., Prasad S. K., Patel D. K., Asian Pac. J. Trop. Biomed., 2012, 2, 660-664
[10]	Alfredo C. C., Luan C. D., Francois S., Louis G., Hormoz M., Maria H., Lana P., Christine P., Vito P., Julian A., Bioorg. Med. Chem. Lett., 2003, 13, 2419-2422
[11]	Chen Y. F., Kuo P. C., Chan H. H., Kuo I. J., Lin F. W., Su C. R., Yang M. L., Li D. T., Wu T. S., J. Nat. Prod., 2010, 73, 1993-1998
[12]	Wu S., Fu Y. S., Yan R. B., Wu Y. F., Lei X. P., Ye X. S., Tetrahedron,2010, 66, 3433-3440
[13]	Brahmbhatt K. G., Ahmed N., Sabde S., Mitra D., Singh I. P., Bhutani K. K., Bioorg. Med. Chem. Lett., 2010, 20, 4416-4419
[14]	Liu L., Yang Q., Yu H., Li J. L., Pei Y. N., Zhu H. J., Li Z. Q., Wang X. K., Tetrahedron,2015, 71, 3296-3302
[15]	Zhu H. J., Liu L., Yang Q., Chem. J. Chinese Universities, 2015, 36(8), 1559-1562
	(朱华结, 刘莉, 杨芹. 高等学校化学学报, 2015, 36(8), 1559-1562)
[16]	Zhu H.J., Organic Stereochemistry-Experimental and Computational Methods, Wiley-VCH(Verlag GmbH & Co. KGaA Weimheim), Weimheim, 2015, 57-115
[17]	Zhu H. J., Modern Organic Stereochemistry, Science Press of China, Beijing, 2009, 283-315
	(朱华结. 现代有机立体化学, 北京: 科学出版社, 2009, 283-315)
[18]	Hu D. B., Zhou B. D., Chem. J. Chinese Universities, 2016, 37(11), 1993-1998
	(胡栋宝, 周北斗. 高等学校化学学报, 2016, 37(11), 1993-1998)
[19]	Abramyants M. G., Lomov D. A., Zavyazkina T. I., Russ. J. Org. Chem., 2016, 52, 1610-1615
[20]	Kamal A., Tangella Y., Manasa K. L., Sathish M., Srinivasulu V., Chetna J., Alarifi A., Org. Biomol. Chem., 2015, 13, 8652-8662
[21]	Kamal A., Sathish M., Nayak V. L., Srinivasulu V., Kavitha B., Tangella Y., Thummuri D., Bagul C., Shankaraiah N., Nagesh N., Bio. Med. Chem., 2015, 23, 5511-5526
[22]	Kamal A., Srinivasulu V., Nayak V. L., Sathish M., Shankaraiah N., Bagul C., Reddy N. V. S., Rangaraj N., Nagesh N., Chem. Med. Chem., 2014, 9, 2084-2098
[23]	Gatta F., Misiti D., J. Heterocycl. Chem., 1989, 26, 537-539
[24]	Cao R H., Peng W. L., Chen H. S., Hou X. R., Guan H. J., Chen Q., Ma Y., Xu A. L., Eur. J. Med. Chem., 2005, 40, 249-257
[25]	Sun R. Q., Liu R., Zhou C., Ren Z. H., Guo L., Ma Q., Fan W. X., Qiu L. Q., Yu H. J., Shao G., Cao R H., Med. Chem. Comm., 2015, 6, 2170-2174
[26]	Kamal A., Sathish M., Nayak V. L., Srinivasulu V., Kavitha B., Tangella Y., Thummuri D., Bagul C., Shankaraiah N., Nagesh N., Bio. Med. Chem., 2015, 23, 5511-5526
[27]	Barbosa V. A., Formagio A. S. N., Savariz F. C., Foglio M. A., Spindola H. M., Carvalho J. E., Meyer E., Sarragiotto M. H., Bio. Med. Chem., 2011, 19, 6400-6408
[28]	Abranyi B. P., Dancso A., Frigyes D., Volk B., Keglevich G., Milen M., Tetrahedron,2014, 70, 5711-5719
[29]	Zhang L., Deng X. S., Wu J. F., Meng G. P., Liu C. C., Chen G. Z., Zhao Q. C., Hu C., Chem. Res. Chinese Universities, 2017, 33(3), 365-372
[30]	Yang J. J., Wang M., Li X., Fan N. N., Xue L. M., Li H., Tian C., Wang X. W., Liu J. Y., Zhang Z. L., Chem. Res. Chinese Universities, 2017, 33(4), 559-568

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