新型葡萄糖-2, 5-二酮哌嗪衍生物的设计、合成与细胞毒活性

doi:10.11978/2022140

Abstract

Abstract:

Exploring the cytotoxic compounds from marine natural products is one of the most important tasks for the discovery of anticancer agent in recent years. In this study, based on the marine natural product Piperafizine B, fourteen novel glycosyl-2, 5-diketopiperazine derivatives (1a-i, 2a-f) have been designed and synthesized by the glycosylation on the side phenol group at the 6-position of the 2, 5-diketopiperizine ring. The solubilities of the derivatives are obviously improved in both DMSO (dimethyl sulfoxide, 1.5~27.9mg·mL^-1) and phosphate buffer (0.1~0.9mg·mL^-1, pH=7.4). The cytotoxicity results show that some of the derivatives present good activities with the IC₅₀ values ranging from 1.0~9.1μmol·L^-1, and exhibit selective inhibitory activities on Huh-7 cell lines. Among the derivatives, compound 1c has the best inhibitory abilities on the cell lines K562, A549 and Huh-7 with an IC₅₀values at 1.0, 3.6 and 3.3μmol·L^-1, respectively, while compounds 2a-f have no observable cytotoxicity.

Key words: marine natural product, 2, 5-dikeropiperazine derivative, glucose, modification, cytotoxicity

LIAO Shengrong, XU Huayan, LI Xiaolin, LIU Yonghong. Design, synthesis and cytotoxicity of novel glycosyl-2, 5-diketopiperazine derivatives[J].Journal of Tropical Oceanography, 2023, 42(3): 174-185.

Figures/Tables 7

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References 28

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化合物	溶解度/(mg·mL^-1)
化合物	C_DMSO	C_缓冲液
1a	21.5	0.9
1b	11.8	0.4
1c	13.9	0.2
1d	17.0	0.9
1e	12.2	0.5
1f	18.0	0.6
1g	21.2	0.8
1h	17.6	0.5
1i	27.9	0.2
2a	18.3	0.6
2b	12.6	0.1
2c	5.70	0.3
2d	7.20	0.8
2e	1.50	0.2
Piperafizine B	0.10	0.05

化合物	IC₅₀/(μmol·mL^-1)
化合物	K562	A549	Huh-7
1a	4.5±0.8	5.2±0.6	3.9±0.9
1b	>10	>10	>10
1c	1.0±0.08	3.6±0.2	3.3±0.4
1d	>10	>10	>10
1e	>10	>10	>10
1f	>10	>10	4.2±0.6
1g	>10	2.9±0.2	3.6±0.6
1h	>10	>10	>10
1i	9.1±1.0	>10	4.5±0.5
2a-e	>10	>10	>10
Piperafizine B	>10	>10	>10
Taxol	0.003±0.0002	0.002±0.0008	0.007±0.0005

Design, synthesis and cytotoxicity of novel glycosyl-2, 5-diketopiperazine derivatives

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