Synthesis and anti-tumor activity of Z-Gly-Pro-OH-podophyllotoxin derivatives

LIANG Guangping; YANG Jun; WU Yunqiu; WAN Luping; RUAN Lijun; SONG Zhijun

doi:10.11665/j.issn.1000-5048.20220105

Journal of China Pharmaceutical University > 2022 > 53(1): 32-40. > DOI: 10.11665/j.issn.1000-5048.20220105

LIANG Guangping, YANG Jun, WU Yunqiu, WAN Luping, RUAN Lijun, SONG Zhijun. Synthesis and anti-tumor activity of Z-Gly-Pro-OH-podophyllotoxin derivatives[J]. Journal of China Pharmaceutical University, 2022, 53(1): 32-40. DOI: 10.11665/j.issn.1000-5048.20220105

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Synthesis and anti-tumor activity of Z-Gly-Pro-OH-podophyllotoxin derivatives

1.
Department of Pharmacy, Zunyi Medical and Pharmaceutical College, Zunyi 563006
2.
National Engineering Laboratory of Southwest Endangered Medicinal Resources Development, Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China

Funds: This study was supported by Guizhou Vocational Education Quality Improvement Project (No. [2019]7) and the Science and Technology Project of Zunyi City (No. [2018]37)

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Received Date: October 07, 2021
Revised Date: December 15, 2021

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Abstract

Ten novel podophyllotoxin derivatives (IIIa-IIIi and IV) were synthesized by three-step reactions using podophyllotoxin and N-benzyloxycarbonyl glycine-L-proline as raw material. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR and MS. MTT method was used to test anti-tumor activity of the target compounds on HepG2, THP-1, HeLa and MCF-7 cells. The results showed that all the target compounds had inhibitory activity against HepG2, THP-1, HeLa and MCF-7 cells, and the inhibitory activity of IIIa on HepG2 cells was the most prominent with an IC₅₀ value of 0.58 nmol/L. The binding mode of compound IIIa and FAPα was studied by molecular docking. Compound IIIa could bind to multiple sites of FAPα enzyme.
- podophyllotoxin,
- derivative,
- synthesis,
- anti-tumor,
- Z-Gly-Pro-OH

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[1]	. Biomolecules，2021，11（4）：603.
[2]	Han HW，Lin HY，He DL，et al. Novel podophyllotoxin derivatives as potential tubulin inhibitors：design，synthesis，and antiproliferative activity evaluation［J］. Chem Biodivers，2018，15（11）：e1800289. doi：10.1002/cbdv.201800289.
[3]	Xu H，Lv M，Tian X. A review on hemisynthesis，biosynthesis，biological activities，mode of action，and structure-activity relationship of podophyllotoxins：2003-2007［J］. Curr Med Chem，2009，16（3）：327-349.
[4]	Shi JF，Wei XY，Wu P，et al. Research progress on enzyme activated antitumor prodrugs based on FAP［J］. Drugs Clin（现代药物与临床），2019，34（10）：3182-3186.
[5]	Garin-Chesa P，Old LJ，Rettig WJ. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers［J］. Proc Natl Acad Sci U S A，1990，87（18）：7235-7239.
[6]	Liu GQ. The study of pharmacodynamics and cardiotoxicity for a new targeting anti-tumor candidate compound Z-GP-EPI（新靶向抗肿瘤候选化合物Z-GP-EPI的药效学及心脏毒性考察）［D］. Guangzhou：Jinan University，2015.
[7]	Sun J，Yang D，Cui SH，et al. Enhanced anti-tumor efficiency of gemcitabine prodrug by FAPα-mediated activation［J］. Int J Pharm，2019，559：48-57.
[8]	Deng LJ，Wang LH，Peng CK，et al. Fibroblast activation protein α activated tripeptide bufadienolide antitumor prodrug with reduced cardiotoxicity［J］. J Med Chem，2017，60（13）：5320-5333.
[9]	Chai XP. Evaluation of anti-tumor efficacy of FAPaerfa5-activated prodrugs of BF211 in vitro and in vivo（FAPα激活式BF211系列前药的体内外抗肿瘤药效评价）［D］. Shanghai：East China Normal University，2017.
[10]	Zhang SJ，Zhu X，Xu YG. Study on structure-activity relationship of podophyllotoxin derivatives and ideas for the development of related new drugs［J］. Prog Pharm Sci（药学进展），2012，36（11）：494-500.
[11]	Liang GP，Huang YM，Huang QZ，et al. Virtual design of FAPα-activated anti-tumor prodrug of podophyllotoxin［J］. Hans J Med Chem（药物化学），2021，9（2）：28-34.
[12]	Zhang ZG，Zhang YH，Ji H，et al. Design，synthesis and antiasthmatic activities of NO-donatingseratrodast derivatives［J］. Acta Pharm Sin（药学学报），2004，39（9）：705-710.
[13]	Zheng JH. Study on chemical constituents of Diphylleia sinensis Li.（窝儿七化学成分的研究）［D］. Xi''an：Shaanxi University of Science & Technology，2012.

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