Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer

Jing Liu; Qi He; Jiaoli Ding; Zhipeng Zhang; Weixin Zhou; Saisai Xie

doi:doi:10.11648/j.bmb.20180304.11

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Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer

Jing Liu, Qi He, Jiaoli Ding, Zhipeng Zhang, Weixin Zhou, Saisai Xie

Published in Biochemistry and Molecular Biology (Volume 3, Issue 4)

Received: 16 November 2018 Accepted: 6 December 2018 Published: 18 December 2018

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Abstract

Aim: Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, showed many biological activities related to the treatment of cancer. However, the comparatively weak activity hinders its further application in clinical. Therefore, the aim of the present study was design and synthesis of a series of novel osthole derivatives by introducing different secondary amine groups at 7-O position of coumarin ring to improve its anticancer activity. Method: After the demethylation of osthole, the target derivatives 4a-l were successfully synthesized through two steps in high yield. The structures of the synthesized compounds were confirmed by 1H and 13C NMR. The antiproliferative activity of these compounds was evaluated against four selected cancer cell lines (SGC7901, MCF-7, HCT116 and HepG2) using MTT method, and the most potent compound was selected for Hoechst 333258 staining assay to further investigate its possible mechanism on cancer cells. Results: Twelve osthole derivatives were synthesized and their structures were identified. Biological studies showed that most of them showed moderate to good growth inhibition against all the tested cancer cells. Especially, compound 4l displayed the most potent activity with IC₅₀ values of 37.57 μM, 25.12 μM, 46.54 μM and 18.39 μM against SCG7901, HCT116, MCF-7 and HepG2, respectively, which was more potent than those of its parent compound osthole and the anticancer agent 5-Fu. The Hoechst 33258 staining assay revealed that compound 4l could induce cell apoptosis in HepG2 cells. Conclusion: The modification of osthole to improve its activity is feasible, and compound 4l can be considered as a potential agent for the treatment of cancer.

Published in	Biochemistry and Molecular Biology (Volume 3, Issue 4)
DOI	10.11648/j.bmb.20180304.11
Page(s)	56-62
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2018. Published by Science Publishing Group

Keywords

Osthole, Anticancer Activity, Synthesis, Apoptosis, Coumarin

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APA Style

Jing Liu, Qi He, Jiaoli Ding, Zhipeng Zhang, Weixin Zhou, et al. (2018). Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochemistry and Molecular Biology, 3(4), 56-62. https://doi.org/10.11648/j.bmb.20180304.11

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ACS Style

Jing Liu; Qi He; Jiaoli Ding; Zhipeng Zhang; Weixin Zhou, et al. Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochem. Mol. Biol. 2018, 3(4), 56-62. doi: 10.11648/j.bmb.20180304.11

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AMA Style

Jing Liu, Qi He, Jiaoli Ding, Zhipeng Zhang, Weixin Zhou, et al. Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochem Mol Biol. 2018;3(4):56-62. doi: 10.11648/j.bmb.20180304.11

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@article{10.11648/j.bmb.20180304.11,
  author = {Jing Liu and Qi He and Jiaoli Ding and Zhipeng Zhang and Weixin Zhou and Saisai Xie},
  title = {Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer},
  journal = {Biochemistry and Molecular Biology},
  volume = {3},
  number = {4},
  pages = {56-62},
  doi = {10.11648/j.bmb.20180304.11},
  url = {https://doi.org/10.11648/j.bmb.20180304.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bmb.20180304.11},
  abstract = {Aim: Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, showed many biological activities related to the treatment of cancer. However, the comparatively weak activity hinders its further application in clinical. Therefore, the aim of the present study was design and synthesis of a series of novel osthole derivatives by introducing different secondary amine groups at 7-O position of coumarin ring to improve its anticancer activity. Method: After the demethylation of osthole, the target derivatives 4a-l were successfully synthesized through two steps in high yield. The structures of the synthesized compounds were confirmed by 1H and 13C NMR. The antiproliferative activity of these compounds was evaluated against four selected cancer cell lines (SGC7901, MCF-7, HCT116 and HepG2) using MTT method, and the most potent compound was selected for Hoechst 333258 staining assay to further investigate its possible mechanism on cancer cells. Results: Twelve osthole derivatives were synthesized and their structures were identified. Biological studies showed that most of them showed moderate to good growth inhibition against all the tested cancer cells. Especially, compound 4l displayed the most potent activity with IC50 values of 37.57 μM, 25.12 μM, 46.54 μM and 18.39 μM against SCG7901, HCT116, MCF-7 and HepG2, respectively, which was more potent than those of its parent compound osthole and the anticancer agent 5-Fu. The Hoechst 33258 staining assay revealed that compound 4l could induce cell apoptosis in HepG2 cells. Conclusion: The modification of osthole to improve its activity is feasible, and compound 4l can be considered as a potential agent for the treatment of cancer.},
 year = {2018}
}

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TY  - JOUR
T1  - Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer
AU  - Jing Liu
AU  - Qi He
AU  - Jiaoli Ding
AU  - Zhipeng Zhang
AU  - Weixin Zhou
AU  - Saisai Xie
Y1  - 2018/12/18
PY  - 2018
N1  - https://doi.org/10.11648/j.bmb.20180304.11
DO  - 10.11648/j.bmb.20180304.11
T2  - Biochemistry and Molecular Biology
JF  - Biochemistry and Molecular Biology
JO  - Biochemistry and Molecular Biology
SP  - 56
EP  - 62
PB  - Science Publishing Group
SN  - 2575-5048
UR  - https://doi.org/10.11648/j.bmb.20180304.11
AB  - Aim: Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, showed many biological activities related to the treatment of cancer. However, the comparatively weak activity hinders its further application in clinical. Therefore, the aim of the present study was design and synthesis of a series of novel osthole derivatives by introducing different secondary amine groups at 7-O position of coumarin ring to improve its anticancer activity. Method: After the demethylation of osthole, the target derivatives 4a-l were successfully synthesized through two steps in high yield. The structures of the synthesized compounds were confirmed by 1H and 13C NMR. The antiproliferative activity of these compounds was evaluated against four selected cancer cell lines (SGC7901, MCF-7, HCT116 and HepG2) using MTT method, and the most potent compound was selected for Hoechst 333258 staining assay to further investigate its possible mechanism on cancer cells. Results: Twelve osthole derivatives were synthesized and their structures were identified. Biological studies showed that most of them showed moderate to good growth inhibition against all the tested cancer cells. Especially, compound 4l displayed the most potent activity with IC50 values of 37.57 μM, 25.12 μM, 46.54 μM and 18.39 μM against SCG7901, HCT116, MCF-7 and HepG2, respectively, which was more potent than those of its parent compound osthole and the anticancer agent 5-Fu. The Hoechst 33258 staining assay revealed that compound 4l could induce cell apoptosis in HepG2 cells. Conclusion: The modification of osthole to improve its activity is feasible, and compound 4l can be considered as a potential agent for the treatment of cancer.
VL  - 3
IS  - 4
ER  -

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Author Information

Jing Liu

School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China
Qi He

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China
Jiaoli Ding

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China
Zhipeng Zhang

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China
Weixin Zhou

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China
Saisai Xie

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China

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APA Style

Jing Liu, Qi He, Jiaoli Ding, Zhipeng Zhang, Weixin Zhou, et al. (2018). Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochemistry and Molecular Biology, 3(4), 56-62. https://doi.org/10.11648/j.bmb.20180304.11

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ACS Style

Jing Liu; Qi He; Jiaoli Ding; Zhipeng Zhang; Weixin Zhou, et al. Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochem. Mol. Biol. 2018, 3(4), 56-62. doi: 10.11648/j.bmb.20180304.11

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AMA Style

Jing Liu, Qi He, Jiaoli Ding, Zhipeng Zhang, Weixin Zhou, et al. Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer. Biochem Mol Biol. 2018;3(4):56-62. doi: 10.11648/j.bmb.20180304.11

Copy | Download

@article{10.11648/j.bmb.20180304.11,
  author = {Jing Liu and Qi He and Jiaoli Ding and Zhipeng Zhang and Weixin Zhou and Saisai Xie},
  title = {Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer},
  journal = {Biochemistry and Molecular Biology},
  volume = {3},
  number = {4},
  pages = {56-62},
  doi = {10.11648/j.bmb.20180304.11},
  url = {https://doi.org/10.11648/j.bmb.20180304.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bmb.20180304.11},
  abstract = {Aim: Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, showed many biological activities related to the treatment of cancer. However, the comparatively weak activity hinders its further application in clinical. Therefore, the aim of the present study was design and synthesis of a series of novel osthole derivatives by introducing different secondary amine groups at 7-O position of coumarin ring to improve its anticancer activity. Method: After the demethylation of osthole, the target derivatives 4a-l were successfully synthesized through two steps in high yield. The structures of the synthesized compounds were confirmed by 1H and 13C NMR. The antiproliferative activity of these compounds was evaluated against four selected cancer cell lines (SGC7901, MCF-7, HCT116 and HepG2) using MTT method, and the most potent compound was selected for Hoechst 333258 staining assay to further investigate its possible mechanism on cancer cells. Results: Twelve osthole derivatives were synthesized and their structures were identified. Biological studies showed that most of them showed moderate to good growth inhibition against all the tested cancer cells. Especially, compound 4l displayed the most potent activity with IC50 values of 37.57 μM, 25.12 μM, 46.54 μM and 18.39 μM against SCG7901, HCT116, MCF-7 and HepG2, respectively, which was more potent than those of its parent compound osthole and the anticancer agent 5-Fu. The Hoechst 33258 staining assay revealed that compound 4l could induce cell apoptosis in HepG2 cells. Conclusion: The modification of osthole to improve its activity is feasible, and compound 4l can be considered as a potential agent for the treatment of cancer.},
 year = {2018}
}

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TY  - JOUR
T1  - Design, Synthesis and Biological Evaluation of Novel Osthole Derivatives as Potential Agents for the Treatment of Cancer
AU  - Jing Liu
AU  - Qi He
AU  - Jiaoli Ding
AU  - Zhipeng Zhang
AU  - Weixin Zhou
AU  - Saisai Xie
Y1  - 2018/12/18
PY  - 2018
N1  - https://doi.org/10.11648/j.bmb.20180304.11
DO  - 10.11648/j.bmb.20180304.11
T2  - Biochemistry and Molecular Biology
JF  - Biochemistry and Molecular Biology
JO  - Biochemistry and Molecular Biology
SP  - 56
EP  - 62
PB  - Science Publishing Group
SN  - 2575-5048
UR  - https://doi.org/10.11648/j.bmb.20180304.11
AB  - Aim: Osthole, an ingredient of Traditional Chinese Medicine (TCM) from natural product Cnidium monnieri (L.) Cusson, showed many biological activities related to the treatment of cancer. However, the comparatively weak activity hinders its further application in clinical. Therefore, the aim of the present study was design and synthesis of a series of novel osthole derivatives by introducing different secondary amine groups at 7-O position of coumarin ring to improve its anticancer activity. Method: After the demethylation of osthole, the target derivatives 4a-l were successfully synthesized through two steps in high yield. The structures of the synthesized compounds were confirmed by 1H and 13C NMR. The antiproliferative activity of these compounds was evaluated against four selected cancer cell lines (SGC7901, MCF-7, HCT116 and HepG2) using MTT method, and the most potent compound was selected for Hoechst 333258 staining assay to further investigate its possible mechanism on cancer cells. Results: Twelve osthole derivatives were synthesized and their structures were identified. Biological studies showed that most of them showed moderate to good growth inhibition against all the tested cancer cells. Especially, compound 4l displayed the most potent activity with IC50 values of 37.57 μM, 25.12 μM, 46.54 μM and 18.39 μM against SCG7901, HCT116, MCF-7 and HepG2, respectively, which was more potent than those of its parent compound osthole and the anticancer agent 5-Fu. The Hoechst 33258 staining assay revealed that compound 4l could induce cell apoptosis in HepG2 cells. Conclusion: The modification of osthole to improve its activity is feasible, and compound 4l can be considered as a potential agent for the treatment of cancer.
VL  - 3
IS  - 4
ER  -

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