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Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors
A series of novel amide-linked 18β-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30–COOH of 18β-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050490/ https://www.ncbi.nlm.nih.gov/pubmed/35496614 http://dx.doi.org/10.1039/d0ra00681e |
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author | Cai, Dong Zhang, Zhi hua Chen, Yu Ruan, Chao Li, Sheng qiang Chen, Shi qin Chen, Lian shan |
author_facet | Cai, Dong Zhang, Zhi hua Chen, Yu Ruan, Chao Li, Sheng qiang Chen, Shi qin Chen, Lian shan |
author_sort | Cai, Dong |
collection | PubMed |
description | A series of novel amide-linked 18β-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30–COOH of 18β-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-7, and PC-3 cell lines by MTT assay. Besides, some compounds with electron-withdrawing groups on phenyl moieties exhibited noticeable antiproliferative activity. The most potent compound 4a was also found to be non-toxic to normal human hepatocytes LO2 cells. The compound 4a exhibited moderate inhibitory activity against wild-type ALK with an IC(50) value of 203.56 nM and relatively weak potent activity to c-Met (IC(50) > 1000 nM). Molecular docking studies were performed to explore the diversification in bonding patterns between the compound 4a and Crizotinib. |
format | Online Article Text |
id | pubmed-9050490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90504902022-04-29 Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors Cai, Dong Zhang, Zhi hua Chen, Yu Ruan, Chao Li, Sheng qiang Chen, Shi qin Chen, Lian shan RSC Adv Chemistry A series of novel amide-linked 18β-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30–COOH of 18β-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-7, and PC-3 cell lines by MTT assay. Besides, some compounds with electron-withdrawing groups on phenyl moieties exhibited noticeable antiproliferative activity. The most potent compound 4a was also found to be non-toxic to normal human hepatocytes LO2 cells. The compound 4a exhibited moderate inhibitory activity against wild-type ALK with an IC(50) value of 203.56 nM and relatively weak potent activity to c-Met (IC(50) > 1000 nM). Molecular docking studies were performed to explore the diversification in bonding patterns between the compound 4a and Crizotinib. The Royal Society of Chemistry 2020-03-23 /pmc/articles/PMC9050490/ /pubmed/35496614 http://dx.doi.org/10.1039/d0ra00681e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Cai, Dong Zhang, Zhi hua Chen, Yu Ruan, Chao Li, Sheng qiang Chen, Shi qin Chen, Lian shan Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title | Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title_full | Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title_fullStr | Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title_full_unstemmed | Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title_short | Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
title_sort | design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel alk inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050490/ https://www.ncbi.nlm.nih.gov/pubmed/35496614 http://dx.doi.org/10.1039/d0ra00681e |
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