Cargando…
Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response
A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a(1)−3d(6)) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tum...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082043/ https://www.ncbi.nlm.nih.gov/pubmed/35539175 http://dx.doi.org/10.1039/c8ra04640a |
_version_ | 1784703123889061888 |
---|---|
author | Kuang, Wen-Bin Huang, Ri-Zhen Fang, Yi-Lin Liang, Gui-Bin Yang, Chen-Hui Ma, Xian-Li Zhang, Ye |
author_facet | Kuang, Wen-Bin Huang, Ri-Zhen Fang, Yi-Lin Liang, Gui-Bin Yang, Chen-Hui Ma, Xian-Li Zhang, Ye |
author_sort | Kuang, Wen-Bin |
collection | PubMed |
description | A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a(1)−3d(6)) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results showed that the representative compound 3a(1) exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a(1) may exert antitumor activity by the up-regulation of Bax, intracellular Ca(2+) release, ROS generation, p21, p27 and p53, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, and inhibition of CDK activity. |
format | Online Article Text |
id | pubmed-9082043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90820432022-05-09 Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response Kuang, Wen-Bin Huang, Ri-Zhen Fang, Yi-Lin Liang, Gui-Bin Yang, Chen-Hui Ma, Xian-Li Zhang, Ye RSC Adv Chemistry A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives (3a(1)−3d(6)) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results showed that the representative compound 3a(1) exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a(1) may exert antitumor activity by the up-regulation of Bax, intracellular Ca(2+) release, ROS generation, p21, p27 and p53, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, and inhibition of CDK activity. The Royal Society of Chemistry 2018-07-06 /pmc/articles/PMC9082043/ /pubmed/35539175 http://dx.doi.org/10.1039/c8ra04640a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Kuang, Wen-Bin Huang, Ri-Zhen Fang, Yi-Lin Liang, Gui-Bin Yang, Chen-Hui Ma, Xian-Li Zhang, Ye Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title | Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title_full | Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title_fullStr | Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title_full_unstemmed | Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title_short | Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
title_sort | design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1h-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082043/ https://www.ncbi.nlm.nih.gov/pubmed/35539175 http://dx.doi.org/10.1039/c8ra04640a |
work_keys_str_mv | AT kuangwenbin designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT huangrizhen designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT fangyilin designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT liangguibin designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT yangchenhui designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT maxianli designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse AT zhangye designsynthesisandpharmacologicalevaluationofnovel2chloro31hbenzodimidazol2ylquinolinederivativesasantitumoragentsinvitroandinvivoantitumoractivitycellcyclearrestandapoptoticresponse |