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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-...

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Detalles Bibliográficos
Autores principales: Cai, Dong, Zhang, Zhi hua, Chen, Yu, Ruan, Chao, Li, Sheng qiang, Chen, Shi qin, Chen, Lian shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
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.
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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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