异戊烯基和香叶基取代的呫吨酮的合成与生物活性研究

doi:10.5246/jcps.2020.08.053

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (8): 564-576.DOI: 10.5246/jcps.2020.08.053

异戊烯基和香叶基取代的呫吨酮的合成与生物活性研究

周北斗^1*, 俞紫涵¹, 童玉贵², 李佳莉¹, 黄堡城¹, 魏蓉蓉¹, 翁智敏¹, 王欣¹, 阮志鹏¹, 林健¹, 许彩红³, 刘建波⁴

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. 莆田出入境检验检疫局, 福建莆田 351100
3. 莆田学院附属医院医疗集团, 福建莆田 351100
4. 联化科技股份有限公司, 浙江台州 318020

收稿日期:2020-01-12 修回日期:2020-04-20 出版日期:2020-08-31 发布日期:2020-05-16
通讯作者: Tel.: +86-13205940072, E-mail: beidouzhou@ptu.edu.cn
基金资助:
Leading Project of Fujian Provincial Department of Science and Technology (Grant No. 2018Y0072).

Synthesis of prenylated and geranylated xanthones and their bioactivities

Beidou Zhou^1*, Zihan Yu¹, Yugui Tong², Jiali Li¹, Baocheng Huang¹, Rongrong Wei¹, Zhimin Weng¹, Xin Wang¹, Zhipeng Ruan¹, Jian Lin¹, Caihong Xu³, Jianbo Liu⁴

1. School of Pharmacy and Medical Technology, Putian University; Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine (Putian University), Fujian Province University, Putian 351100, China
2. Putian Entry-exit Inspection and Quarantine Bureau, Putian 351100, China
3. The Affiliated Hospital (Group) of Putian University, Putian 351100, China
4. Lianhe Chemical Technology Co., Ltd., Taizhou 318020, China

Received:2020-01-12 Revised:2020-04-20 Online:2020-08-31 Published:2020-05-16
Contact: Tel.: +86-13205940072, E-mail: beidouzhou@ptu.edu.cn
Supported by:
Leading Project of Fujian Provincial Department of Science and Technology (Grant No. 2018Y0072).

摘要/Abstract

摘要：

通过两步反应, 合成了9个异戊烯基和香叶基取代的呫吨酮类化合物, 总产率在11%到36%之间。所有的化合物均为首次报道。然后对化合物1–9的全部或者部分抗肿瘤、抑制酪氨酸酶、抑制胰脂肪酶、抗真菌和抗菌活性进行评估。化合物9显示出明显的抗肿瘤活性, 其对人乳腺癌细胞MCF-7和MDA-MB-231的细胞毒性均大于顺铂。化合物1–4和6–7也显示出一定的上述除了抗肿瘤以外的活性。这些结果显示化合物1–4、6–7和9是很有希望的先导化合物, 可用于进一步结构修饰。

关键词: 呫吨酮, 抗肿瘤活性, 抑制酪氨酸酶, 抗真菌活性, 抗菌活性

Abstract:

Nine prenylated and geranylated xanthones were synthesized in two steps with total yields ranging from 11% to 36%. All of the compounds were first reported. Then, the antitumor, anti-tyrosinase, anti-pancreatic lipase,antifungal and antibacterial activities of all or part of compounds 1–9 were evaluated. Compound 9 exhibited clear antitumor activity, and its cytotoxicity against MCF-7 and MDA-MB-231 cells was stronger compared with cisplatin. Compounds 1–4 and 6–7 alsoexhibited certain activity other than the antitumor activity described above. These results demonstrated that compounds 1–4, 6–7and 9 were very promising leads for further structural modification.

Key words: Xanthone, Antitumor activity, Anti-tyrosinase, Antifungal activity, Antibacterial activity

中图分类号:

R915.4

Supporting:

周北斗, 俞紫涵, 童玉贵, 李佳莉, 黄堡城, 魏蓉蓉, 翁智敏, 王欣, 阮志鹏, 林健, 许彩红, 刘建波. 异戊烯基和香叶基取代的呫吨酮的合成与生物活性研究[J]. 中国药学(英文版), 2020, 29(8): 564-576.

Beidou Zhou, Zihan Yu, Yugui Tong, Jiali Li, Baocheng Huang, Rongrong Wei, Zhimin Weng, Xin Wang, Zhipeng Ruan, Jian Lin, Caihong Xu, Jianbo Liu. Synthesis of prenylated and geranylated xanthones and their bioactivities[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(8): 564-576.

参考文献

[1] Koh, J.J.; Zou, H.X.; Mukherjee, D.; Lin, S.M.; Lim, F.H.; Tan, J.K.; Tan, D.Z.; Stocker, B.L.; Timmer, M.S.M.; Corkran, H.M.; Lakshminarayanan, R.; Tan, D.T.H.; Cao, D.R.; Beuerman, R.W.; Dick, T.; Liu, S.P. Amphiphilic xanthones as a potent chemical entity of anti-mycobacterial agents with membrane-targeting properties. Eur. J. Med. Chem. 2016, 123, 684-703.

[2] Li, D.H.; Li, C.X.; Jia, C.C.; Sun, Y.T.; Xue, C.M.; Bai, J.; Hua, H.M.; Liu, X.Q.; Li, Z.L. Xanthones from Garcinia paucinervis with in vitro anti-proliferative activity against HL-60 cells. Arch. Pharm. Res. 2016, 39, 172-177.

[3] Reyes-Chilpa, R.; Jimenez-Estrada, M.; Estrada-Muñiz, E. Antifungal xanthones from Calophyllum brasiliensis heartwood. J. Chem. Ecol. 1997, 23, 1901-1911.

[4] Boonnak, N.; Karalai, C.; Chantrapromma, S.; Ponglimanont, C.; Kanjana-Opas, A.; Chantrapromma, K.; Kato, S. Chromene and prenylated xanthones from the roots of Cratoxylum formosum ssp. pruniflorum. Chem. Pharm. Bull. 2010, 58, 386-389.

[5] Yen, C.T.; Nakagawa-Goto, K.; Hwang, T.L.; Morris-Natschke, S.L.; Bastow, K.F.; Wu, Y.C.; Lee, K.H. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents. Bioorg. Med. Chem. Lett. 2012, 22, 4018-4022.

[6] Chairungsrilerd, N.; Takeuchi, K.; Ohizumi, Y.; Nozoe, S.; Ohta, T. Mangostanol, a prenyl xanthone from Garcinia mangostana. Phytochemistry. 1996, 43, 1099-1102.

[7] Zhang, X.J.; Li, X.; Ye, S.F.; Zhang, Y.; Tao, L.; Gao, Y.; Gong, D.D.; Xi, M.Y.; Meng, H.Y.; Zhang, M.Q.; Gao, W.L.; Xu, X.L.; Guo, Q.L.; You, Q.D. Synthesis, SAR and biological evaluation of natural and non-natural hydroxylated and prenylated xanthones as antitumor agents. Med. Chem. 2012, 8, 1012-1025.

[8] Wang, G.H.; Jiang, F.Q.; Duan, Y.H.; Zeng, Z.P.; Chen, F.; Dai, Y.; Chen, J.B.; Liu, J.X.; Liu, J.; Zhou, H.; Chen, H.F.; Zeng, J.Z.; Su, Y.; Yao, X.S.; Zhang, X.K. Targeting truncated retinoid X receptor-α by CF31 induces TNF-α-dependent apoptosis. Cancer Res. 2013, 73, 307-318.

[9] Zhou, B.D.; Zeng, L.L.; Tong, Y.G.; Fang, J.Y.; Ruan, Z.P.; Zeng, X.Y.; Fang, Y.Y.; Xu, G.F.; Hu, D.B. Synthesis and antitumor, antityrosinase and antioxidant activities of xanthone. J. Asian Nat. Prod. Res. 2018, 20, 467-476.

[10] Zhou, B.D.; Wang, X.; Weng, Z.M.; Huang, B.C.; Ma, Z.T.; Yu, B.; Ruan, L.Q.; Hu, D.B. Synthesis and antitumor, antityrosinase, and antiplatelet aggregation activities of xanthone. J. Chin. Pharm. Sci. 2019, 28, 247-256.

[11] Liu, J.; Zhang, J.R.; Wang, H.L.; Liu, Z.J.; Zhang, C.; Jiang, Z.L.; Chen, H.R. Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them. Eur. J. Med. Chem. 2017, 133, 50-61.

[12] Castanheiro, R.A.; Pinto, M.M.; Silva, A.M.; Cravo, S.M.; Gales, L.; Damas, A.M.; Nazareth, N.; Nascimento, M.S.; Eaton, G. Dihydroxyxanthones prenylated derivatives: synthesis, structure elucidation, and growth inhibitory activity on human tumor cell lines with improvement of selectivity for MCF-7. Bioorg. Med. Chem. 2007, 15, 6080-6088.

[13] Nakayama, M.; Eguchi, S.; Hayashi, S.; Tsukayama, M.; Horie, T.; Yamada, T.; Masumura, M. The synthesis of neobavaisoflavone and related compounds. Bull. Chem. Soc. Jpn. 1978, 51, 2398-2400.

[14] Seyedan, A.; Alshawsh, M.A.; Alshagga, M.A.; Koosha, S.; Mohamed, Z. Medicinal plants and their inhibitory activities against pancreatic lipase: a review. Evid. Based Compl. Alt. 2015, 2015, 1-13.

[15] Buchholz, T.; Melzig, M.F. Polyphenolic compounds as pancreatic lipase inhibitors. Planta Med. 2015, 81, 771-783.

[16] Pedras, M.S.C.; Abdoli, A. Methoxycamalexins and related compounds: Syntheses, antifungal activity and inhibition of brassinin oxidase. Bioorg. Med. Chem. 2018, 26, 4461-4469.

[17] Łukowska-Chojnacka, E.; Mierzejewska, J.; Milner-Krawczyk, M.; Bondaryk, M.; Staniszewska, M. Synthesis of novel tetrazole derivatives and evaluation of their antifungal activity. Bioorg. Med. Chem. 2016, 24, 6058-6065.

[18] Dharmaratne, H.R.; Sakagami, Y.; Piyasena, K.G.; Thevanesam, V. Antibacterial activity of xanthones from Garcinia mangostana (L.) and their structure-activity relationship studies. Nat. Prod. Res. 2013, 27, 938-941.

[19] Duangsrisai, S.; Choowongkomon, K.; Bessa, L.J.; Costa, P.M.; Amat, N.; Kijjoa, A. Antibacterial and EGFR-tyrosine kinase inhibitory activities of polyhydroxylated xanthones from Garcinia succifolia. Molecules. 2014, 19, 19923-19934.

异戊烯基和香叶基取代的呫吨酮的合成与生物活性研究

Synthesis of prenylated and geranylated xanthones and their bioactivities

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