Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells

研究成果: 雜誌貢獻文章

摘要

The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.

原文英語
文章編號103119
期刊Bioorganic Chemistry
91
DOIs
出版狀態已發佈 - 十月 1 2019

指紋

Growth Inhibitors
Amides
Prostatic Neoplasms
Cells
Lead compounds
Docks
Molecular modeling
Cell growth
Cell Cycle Checkpoints
Catalytic Domain
Proteins
Apoptosis
Amino Acids
Cell Line
Degradation
Growth
resorcinol
quinoline
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

引用此文

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title = "Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells",
abstract = "The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.",
keywords = "Apoptosis, Cancer, Chaperone, Heat shock protein, Quinoline, Resorcinol",
author = "Kunal Nepali and Lin, {Mei Hsiang} and Chao, {Min Wu} and Peng, {Sheng Jhih} and Hsu, {Kai Cheng} and {Eight Lin}, Tony and Chen, {Mei Chuan} and Lai, {Mei Jung} and Pan, {Shiow Lin} and Liou, {Jing Ping}",
year = "2019",
month = "10",
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doi = "10.1016/j.bioorg.2019.103119",
language = "English",
volume = "91",
journal = "Bioorganic Chemistry",
issn = "0045-2068",
publisher = "Academic Press Inc.",

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AU - Nepali, Kunal

AU - Lin, Mei Hsiang

AU - Chao, Min Wu

AU - Peng, Sheng Jhih

AU - Hsu, Kai Cheng

AU - Eight Lin, Tony

AU - Chen, Mei Chuan

AU - Lai, Mei Jung

AU - Pan, Shiow Lin

AU - Liou, Jing Ping

PY - 2019/10/1

Y1 - 2019/10/1

N2 - The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.

AB - The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.

KW - Apoptosis

KW - Cancer

KW - Chaperone

KW - Heat shock protein

KW - Quinoline

KW - Resorcinol

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JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

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