Design, Synthesis, and Biological Evaluation of Novel Biotinylated Podophyllotoxin Derivatives as Potential Antitumor Agents
Zi, Cheng-Ting1,2,3,4,5; Gao, Yin-Sheng6; Yang, Liu1,2; Feng, Shu-Yun6; Huang, Yue6; Sun, Li6; Jin, Yi5; Xu, Feng-Qing1,2; Dong, Fa-Wu1,2; Li, Yan1,2; Ding, Zhong-Tao5; Zhou, Jun1,2; Jiang, Zi-Hua7; Yuan, Sheng-Tao6; Hu, Jiang-Miao1,2
Corresponding AuthorJiang, Zi-Hua(zjiang@lakeheadu.ca) ; Yuan, Sheng-Tao(cpuYuanst@163.com) ; Hu, Jiang-Miao(hujiangmiao@mail.kib.ac.cn)
2019-06-18
Source PublicationFRONTIERS IN CHEMISTRY
ISSN2296-2646
Volume7Pages:14
AbstractPodophyllotoxin has long been used as an active substance for cytotoxic activity. Fourteen novel biotinylated podophyllotoxin derivatives were designed, synthesized, and evaluated for cytotoxic activity for this study. The synthesized compounds were evaluated for cytotoxic activity in the following human cancer cell lines, SW480, MCF-7, A-549, SMMC-7721, and HL-60 by MTT assay. Most of them exhibited potent cytotoxic effects and compound 15 showed the highest cytotoxic activity among the five cancer cell lines tested, having its IC50 values in the range of 0.13 to 0.84 mu M. Apoptosis analysis revealed that compound 15 caused obvious induction of cell apoptosis. Compound 15 significantly down-regulated the expression level of the marker proteins (caspase-3 and PARP) in H1299 and H1975 cells, activated the transcription of IRE1 alpha, increased the expression of GRP78 and XBP-1s, and finally induced apoptosis of H1299 cells. In vivo studies showed that 15 at a dose of 20 mg/kg suppressed tumor growth of S180 cell xenografts in icr mice significantly. Further molecular docking studies suggested that compound 15 could bind well with the ATPase domain of Topoisomerase-II. These data suggest that compound 15 is a promising agent for cancer therapy deserving further research.
Keywordpodophyllotoxin derivatives biotin anticancer activity synthesis apoptosis
DOI10.3389/fchem.2019.00434
Indexed BySCI
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000471844200001
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/67250
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorJiang, Zi-Hua; Yuan, Sheng-Tao; Hu, Jiang-Miao
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, Yunnan Key Lab Nat Med Chem, Kunming, Yunnan, Peoples R China
3.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing, Jiangsu, Peoples R China
4.China Pharmaceut Univ, Jiangsu Ctr Pharmacodynam Res & Evaluat, Nanjing, Jiangsu, Peoples R China
5.Yunnan Agr Univ, Coll Sci, Key Lab Pu Er Tea Sci, Minist Educ, Kunming, Yunnan, Peoples R China
6.Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Sch Chem Sci & Technol, Kunming, Yunnan, Peoples R China
7.Lakehead Univ, Dept Chem, Thunder Bay, ON, Canada
Recommended Citation
GB/T 7714
Zi, Cheng-Ting,Gao, Yin-Sheng,Yang, Liu,et al. Design, Synthesis, and Biological Evaluation of Novel Biotinylated Podophyllotoxin Derivatives as Potential Antitumor Agents[J]. FRONTIERS IN CHEMISTRY,2019,7:14.
APA Zi, Cheng-Ting.,Gao, Yin-Sheng.,Yang, Liu.,Feng, Shu-Yun.,Huang, Yue.,...&Hu, Jiang-Miao.(2019).Design, Synthesis, and Biological Evaluation of Novel Biotinylated Podophyllotoxin Derivatives as Potential Antitumor Agents.FRONTIERS IN CHEMISTRY,7,14.
MLA Zi, Cheng-Ting,et al."Design, Synthesis, and Biological Evaluation of Novel Biotinylated Podophyllotoxin Derivatives as Potential Antitumor Agents".FRONTIERS IN CHEMISTRY 7(2019):14.
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