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Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin.
Eur J Med Chem. 2020 Feb 01; 187:111971.EJ

Abstract

For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial.

Authors+Show Affiliations

School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China; College of Pharmaceutical Science, Zhejiang Chinese Medical University, 310000, PR China. Electronic address: yqliu@lzu.edu.cn.School of Pharmacy, Lanzhou University, Lanzhou, 730000, PR China.School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31881457

Citation

Yang, Cheng-Jie, et al. "Design, Synthesis and Antineoplastic Activity of Novel 20(S)-acylthiourea Derivatives of Camptothecin." European Journal of Medicinal Chemistry, vol. 187, 2020, p. 111971.
Yang CJ, Li B, Zhang ZJ, et al. Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin. Eur J Med Chem. 2020;187:111971.
Yang, C. J., Li, B., Zhang, Z. J., Gao, J. M., Wang, M. J., Zhao, X. B., Song, Z. L., Liu, Y. Q., Li, H., Chen, Y., Lee, K. H., Morris-Natschke, S. L., & Xu, C. (2020). Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin. European Journal of Medicinal Chemistry, 187, 111971. https://doi.org/10.1016/j.ejmech.2019.111971
Yang CJ, et al. Design, Synthesis and Antineoplastic Activity of Novel 20(S)-acylthiourea Derivatives of Camptothecin. Eur J Med Chem. 2020 Feb 1;187:111971. PubMed PMID: 31881457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin. AU - Yang,Cheng-Jie, AU - Li,Bin, AU - Zhang,Zhi-Jun, AU - Gao,Jian-Mei, AU - Wang,Mei-Juan, AU - Zhao,Xiao-Bo, AU - Song,Zi-Long, AU - Liu,Ying-Qian, AU - Li,Hu, AU - Chen,Yuyuan, AU - Lee,Kuo-Hsiung, AU - Morris-Natschke,Susan L, AU - Xu,Chuanrui, Y1 - 2019/12/13/ PY - 2019/10/30/received PY - 2019/12/01/revised PY - 2019/12/12/accepted PY - 2019/12/28/pubmed PY - 2019/12/28/medline PY - 2019/12/28/entrez KW - Acylthioureas KW - Camptothecin KW - Cytotoxicity KW - Topoisomerase I SP - 111971 EP - 111971 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 187 N2 - For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/31881457/Design,_synthesis_and_antineoplastic_activity_of_novel_20(S)-acylthiourea_derivatives_of_camptothecin L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(19)31123-7 DB - PRIME DP - Unbound Medicine ER -
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