氧杂蒽酮的合成和抗肿瘤、抑制酪氨酸酶和抑制血小板聚集活性研究

doi:10.5246/jcps.2019.04.025

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (4): 247-256.DOI: 10.5246/jcps.2019.04.025

氧杂蒽酮的合成和抗肿瘤、抑制酪氨酸酶和抑制血小板聚集活性研究

周北斗¹, 王欣¹, 翁智敏¹, 黄堡城¹, 马泽通¹, 于博¹, 阮丽琴¹, 胡栋宝^2*

1. 莆田学院药学与医学技术学院, 药物分析与检验医学福建省高校重点实验室, 福建莆田 351100
2. 玉溪师范学院化学生物与环境学院, 云南玉溪 653100

收稿日期:2018-12-03 修回日期:2019-01-26 出版日期:2019-04-30 发布日期:2019-01-30
通讯作者: Tel.: +86-18869712768, E-mail: hudongbao@126.com
基金资助:
Fujian Provincial Department of Science and Technology (Grant No. 2018Y0072).

Synthesis and antitumor, antityrosinase, and antiplatelet aggregation activities of xanthone

Beidou Zhou¹, Xin Wang¹, Zhimin Weng¹, Baocheng Huang¹, Zetong Ma¹, Bo Yu¹, Liqin Ruan¹, Dongbao Hu^2*

1. School of pharmacy and medical technology, Putian university, China; Key laboratory of pharmaceutical analysis and laboratory medicine (Putian university), Fujian province university, Putian 351100, China
2. School of chemical biology and environment, Yuxi normal university, Yuxi 653100, China

Received:2018-12-03 Revised:2019-01-26 Online:2019-04-30 Published:2019-01-30
Contact: Tel.: +86-18869712768, E-mail: hudongbao@126.com
Supported by:
Fujian Provincial Department of Science and Technology (Grant No. 2018Y0072).

摘要/Abstract

摘要：

在当前的研究中, 5个氟取代和3个氯取代的1,3-二羟基氧杂蒽酮(化合物11–18)被一步合成,它们的产率在48%和72%之间。在这8个化合物中, 化合物12和15–18被首次报道。化合物1–19的全部或者部分抗肿瘤、抑制酪氨酸酶和抑制血小板聚集的活性被检测。对于某些特定的肿瘤细胞, 化合物1–2、4、6–7、10–15和19显示出较好的抑制活性, 特别是7位含有2,4-二氟苯基的化合物10显示出较高的抗肿瘤活性。化合物18对酪氨酸酶的抑制率约为22%。在大鼠中, 化合物1–3、6、9、12和18–19明显地抑制由二磷酸腺苷(ADP)诱导的血小板聚集。而且, 化合物2和3的作用最为显著。这些结果显示化合物1–4、6–7、9–15和19是有希望的先导化合物,可用于进一步结构修饰。

关键词: 氧杂蒽酮, 合成, 抗肿瘤, 抑制酪氨酸酶, 抑制血小板聚集

Abstract:

In the present study, five fluorine substituted and three chlorine substituted 1,3-dihydroxyxanthones were synthesized in one step.The yields ranged from 48% to 72%. Among them, compounds 12 and 15–18 were reported for the first time. The antitumor, antityrosinase and antiplatelet aggregation activities of all or part of compounds 1–19 were evaluated. Compounds 1, 2, 4, 6–7, 10–15 and 19 exhibited enhanced cytotoxicity against certain cancer cells. Compound 10,containing 2,4-difluorophenyl at the C7 position, particularly exhibited superior antitumor activity. The inhibition rate of compound 18 against tyrosinase was approximately 22%. Compounds 1–3, 6, 9, 12 and 18, 19 exhibited obvious inhibitory platelet aggregation induced by ADP in rats. Moreover, the effects of compounds 2 and 3 were more pronounced. These results demonstrated that compounds 1–4, 6–7, 9–15 and 19 were promising leads for further structural modification.

Key words: Xanthone, Synthesis, Antitumor, Antityrosinase, Antiplatelet aggregation

中图分类号:

R916

Supporting:

The ¹H NMR spectrum of 5-fluoro-1,3-dihydroxy-9H-xanthen-9-one (11) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 5-fluoro-1,3-dihydroxy-9H-xanthen-9-one (11) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 6-fluoro-1,3-dihydroxy-9H-xanthen-9-one (12) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 6-fluoro-1,3-dihydroxy-9H-xanthen-9-one (12) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 7-fluoro-1,3-dihydroxy-9H-xanthen-9-one (13) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 7-fluoro-1,3-dihydroxy-9H-xanthen-9-one (13) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 8-fluoro-1,3-dihydroxy-9H-xanthen-9-one (14) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 8-fluoro-1,3-dihydroxy-9H-xanthen-9-one (14) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 1,2-difluoro-6,8-dihydroxy-9H-xanthen-9-one (15) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 1,2-difluoro-6,8-dihydroxy-9H-xanthen-9-one (15) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 5-chloro-1,3-dihydroxy-9H-xanthen-9-one (16) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 5-chloro-1,3-dihydroxy-9H-xanthen-9-one (16) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 5,7-dichloro-1,3-dihydroxy-9H-xanthen-9-one (17) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 5,7-dichloro-1,3-dihydroxy-9H-xanthen-9-one (17) (DMSO-d₆, 125 MHz)

The ¹H NMR spectrum of 1,2,4-trichloro-6,8-dihydroxy-9H-xanthen-9-one (18) (DMSO-d₆, 500 MHz)

The ¹³C NMR spectrum of 1,2,4-trichloro-6,8-dihydroxy-9H-xanthen-9-one (18) (DMSO-d₆, 125 MHz)

周北斗, 王欣, 翁智敏, 黄堡城, 马泽通, 于博, 阮丽琴, 胡栋宝. 氧杂蒽酮的合成和抗肿瘤、抑制酪氨酸酶和抑制血小板聚集活性研究[J]. 中国药学(英文版), 2019, 28(4): 247-256.

Beidou Zhou, Xin Wang, Zhimin Weng, Baocheng Huang, Zetong Ma, Bo Yu, Liqin Ruan, Dongbao Hu. Synthesis and antitumor, antityrosinase, and antiplatelet aggregation activities of xanthone[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(4): 247-256.

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氧杂蒽酮的合成和抗肿瘤、抑制酪氨酸酶和抑制血小板聚集活性研究

Synthesis and antitumor, antityrosinase, and antiplatelet aggregation activities of xanthone

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