三甲氧基没食子酸1, 2, 4-噻二唑-3, 5-二酮衍生物的合成及其对HL60细胞增殖的抑制作用

doi:10.3969/j.issn.0253-2417.2020.03.016

Abstract

Abstract:

A series of 1, 2, 4-thiadiazole-3, 5-dione derivatives of trimethoxy gallic acid (4a-4e) were synthesized, and the intermediate products 2, 3 and the target compounds 4a-4e were tested against the proliferation of acute leukemia HL60 by MTT method.The inhibition of cell proliferation, and the synergistic effects of 4b and 4c and the positive control TDZD-8 on the proliferation inhibition of HL60 cells were investigated. The results showed that compounds 2-4 had a certain inhibitory effect on the proliferation of HL60 cells. Among them, compounds 4b and 4c had better inhibitory effects, and their half inhibitory concentrations (IC₅₀) were 10.60 and 6.31 μmol/L, respectively and the IC₅₀ value of TDZD-8 on HL60 cells was 0.30 mmol/L. In addition, 4b and 4c cooperated with TDZD-8 had better proliferation inhibitory effect on the acute leukemia cell line HL60. When the concentrations of 4b and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate of them was 94.45%, and the collaborative index(CI) value of the synergy index was 0.58; when the concentrations of 5c and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate was 98.76% and the CI value was 0.31. It could be seen that the new gallic acid 1, 2, 4-thiadiazole-3, 5-dione derivative could potentially act as the drug leader for treating human acute leukemia.

Key words: gallic acid, 1, 2, 4-thiadiazolidine-3, 5-dione, TDZD-8, HL60, synergistic

CLC Number:

TQ35

Zhiwen QI,Hao ZHOU,Xingying XUE,Yangyang YAN,Chengzhang WANG. Synthesis of 1, 2, 4-Thiadiazole-3, 5-dione Derivatives of Trimethoxy GallicAcid and Its Inhibition of HL60 Cell Line Proliferation[J]. Chemistry and Industry of Forest Products, 2020, 40(3): 123-129.

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References 21

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化合物 compounds	不同浓度时的细胞抑制率inhibitory rate of different concentration/%				IC₅₀¹⁾/ (μmol·L^-1)
化合物 compounds	1.0 μmol/L	5.0 μmol/L	10.0 μmol/L	30.0 μmol/L	IC₅₀¹⁾/ (μmol·L^-1)
2	1.31	8.95	15.5	23.5	＞30.0
3	2.56	6.32	15.2	46.8	＞30.0
4a	3.87	12.2	26.2	55.6	21.3
4b	2.75	20.0	49.8	75.7	10.6
4c	7.25	42.6	95.4	99.5	6.31
4d	4.87	24.6	43.5	65.2	18.6
4e	4.56	12.9	25.6	52.6	27.2

TDZD-8/ (μmol·L^-1)	4b(4c)/ (μmol·L^-1)	TDZD-8+4b			TDZD-8+4c
TDZD-8/ (μmol·L^-1)	4b(4c)/ (μmol·L^-1)	抑制率/% inhibition rate	Fa/%	CI	抑制率/% inhibition rate	Fa/%	CI
0.68	8.0	98.09±10.12	12	0.76	99.80±10.90	11	0.45
0.34	5.0	94.45±14.02	38	0.58	98.76±10.78	39	0.31
0.17	3.5	60.23±7.05	43	0.62	69.67±8.89	53	0.52
0.057	2.5	29.66±6.10	52	0.83	35.81±9.32	59	0.59
0.029	1.2	23.41±7.23	76	0.89	28.32±8.11	79	0.62
0.015	1.0	16.88±4.92	85	0.96	20.23±5.85	84	0.74

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Synthesis of 1, 2, 4-Thiadiazole-3, 5-dione Derivatives of Trimethoxy GallicAcid and Its Inhibition of HL60 Cell Line Proliferation

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