Syntheses and Structure-activity Relationship of Podophyllotoxin Derivatives as Potential Anticancer Drugs

Abstract

Abstract: Thirteen new 4β-substituted podophyllotoxin derivatives 5-17 were synthesizedand their structures were confirmed by IR, MS, ¹H NMRand ESRas well as elementaryanalysis.All new compounds were evaluated for their anticancer activity against mouseleukemia P388 and human stomach carcinoma SGC-7901 cells in vitro- Compounds 5, 7-10exhibited a remarkable inhibition activity against both P388 and SGC-7901 cells.In a struc-ture-activity comparison it was found that 4' -O-demethylpodophyllotoxins 5, 10-13 showeda superior activity to the corresponding 4' -methoxy analogues 6, 14-17 lacking a free OHgroup at C-4'.The replacement of the "-NH-" bridge at C-4 with the "-O-" bridge re-sulted in lowering of the anticancer activity.These results demonstrate the possibility ofconsiderable simplification in the sugar structure of VP-16 and the importance of 4' -phenolichydroxyl group, and suggest further elaboration of 4β-nitrogen-containing substitutlent tooptimize the structure of this class of anticancer compounds.

Key words: Podophyllotoxin, Anticancer, Nitroxyl

CLC Number:

R914.5

TrendMD:

WANG Yan-Guang, TAO Lan, PAN Jian-Lin, SHI Jian-Feng, CHEN Yao-Zu. Syntheses and Structure-activity Relationship of Podophyllotoxin Derivatives as Potential Anticancer Drugs[J]. Chem. J. Chinese Universities, 1997, 18(7): 1061.

[1]	ZHAO Ying, QIAO Ling, ZHAO Guofeng, CHEN Li. Synthesis and Biological Activity of Lycorine Derivatives Containing Malate Ester [J]. Chem. J. Chinese Universities, 2021, 42(9): 2789.
[2]	XUE Xuling,CHEN Jun,ZHANG Ziyou,WANG Mengmeng,Lü Mengdi,HAO Yuanyuan,HU Jiongsheng,GE Chao,SU Zhi,QIAN Yong,LIU Hongke. Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications ^† [J]. Chem. J. Chinese Universities, 2020, 41(2): 243.
[3]	LUO Zewei, WANG Yimin, LIU Kunping, WEI Fujing, LI Yu, DUAN Yixiang. Preparation of a Functionalized Graphene and Its Role as Delivery Carrier for Anti-cancer Drug^† [J]. Chem. J. Chinese Universities, 2016, 37(10): 1900.
[4]	LIU Dan, HU Xiufang, ZHENG Yanyan, PAN He, LUO Shuwei, HONG Fang, ZHAO Wenna, JIANG Meihong, ZHU Yunhui, SHAO Jingwei, WANG Wenfeng. Synthesis of Lipiophilic Cations of Anthraquinone and Their Anticancer Activities^† [J]. Chem. J. Chinese Universities, 2015, 36(6): 1100.
[5]	ZHANG Fada, LIU Yi, XU Jingcheng, LI Shengjuan, WANG Xiunan, SUN Yue, ZHAO Xinluo. Molecular Dynamics Study on Binding Strength and Conformation of Dendrimer-based Drug Delivery Systems^† [J]. Chem. J. Chinese Universities, 2015, 36(6): 1156.
[6]	KUANG Daizhi, FENG Yonglan, YU Jiangxi, ZHANG Fuxing, JIANG Wujiu, PENG Yan, ZHU Xiaoming, TAN Yuxing. Microwave Assisted Solid-state Synthesis, Crystal Structure, Properties of the Coordination Polymer Constructed from Tricyclohexyltin Hydroxide and o-Ferrocenylcarbonyl Benzoic Acid^† [J]. Chem. J. Chinese Universities, 2014, 35(8): 1629.
[7]	ZHANG Zhuoqi, GENG Haoran, XUAN Ruifei, CHEN Minmin, CHEN Hui, LIU Aihui, CAO Xichuan. Fabrication and TXL Anti-cancer Drug Delivery of Magnetic Mesoporous Silica Nanoparticles^† [J]. Chem. J. Chinese Universities, 2014, 35(7): 1509.
[8]	LI Xiaoliu, MA Donglai, YANG Hailong, TAN Guanhai, DU Huiru, WANG Kerang, ZHANG Pingzhu, CHEN Hua. Synthesis, Antitumor Activity and DNA Binding of cridine-polyamine Conjugates^† [J]. Chem. J. Chinese Universities, 2014, 35(6): 1181.
[9]	LIU Haibin, LÜ Ping, PAN Ningning, AI Limei, LIU Yongxiang. Synthesis and In vitro Anticancer Activity of Novel Quinazoline Derivatives Containing Thiosemicarbazone Structure^† [J]. Chem. J. Chinese Universities, 2014, 35(5): 981.
[10]	HAO Hequn, YAO Ping. In Vitro Anticancer Effects of Doxorubicin Loaded BSA-dextran Nanoparticles with Different Molecular Weights of Dextran and Different Dextran Conjugation Degrees^† [J]. Chem. J. Chinese Universities, 2014, 35(3): 652.
[11]	LIU Cheng, ZHENG Yan-Yan, HONG Fang, HU Jian-Da, ZHAO Wen-Na, YUAN Yao-Feng, SHAO Jing-Wei, WANG Wen-Feng. Synthesis and Anticancer Activity Evaluation of Derivatives of Emodin [J]. Chem. J. Chinese Universities, 2013, 34(6): 1408.
[12]	HUANG Yi-Bing, ZHAI Nai-Cui, GAO Gui, CHEN Yu-Xin. Effects of Net Charge on Biological Activities of Alpha-helical Anticancer Peptides [J]. Chem. J. Chinese Universities, 2012, 33(06): 1252.
[13]	HUANG Xiao-Chun, ZHENG Jun-Sheng, CHEN Tian-Feng, ZHANG Yi-Bo, LUO Yi, ZHENG Wen-Jie. Synthesis, Antioxidant and Anticancer Activities of 1,2,5-Selenadiazole Pyrimidine Heterocyclic Derivative ASPO [J]. Chem. J. Chinese Universities, 2012, 33(05): 976.
[14]	CHANG Juan-Juan, WANG Yan, ZHANG Hui-Zhen, ZHOU Cheng-He*, GENG Rong-Xia, JI Qing-Gang. Recent Advances in Researches of Triazole-based Supramolecular Chemistry and Medicinal Drugs [J]. Chem. J. Chinese Universities, 2011, 32(9): 1970.
[15]	JIN Yong-Ri, SHI Xiao-Lei, LI Xu-Wen, ZHAO Xue-Zhong, ZHANG Mu-Chun. Matrix Solid Phase Dispersion for the Extraction of Podophyllotoxin Glucoside and Isopicropodophyllone from Roots of Sinopodophyllum emodi(Wall.) [J]. Chem. J. Chinese Universities, 2011, 32(5): 1054.

Syntheses and Structure-activity Relationship of Podophyllotoxin Derivatives as Potential Anticancer Drugs

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments