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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...

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Autores principales: Kuang, Wen-Bin, Huang, Ri-Zhen, Fang, Yi-Lin, Liang, Gui-Bin, Yang, Chen-Hui, Ma, Xian-Li, Zhang, Ye
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
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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.
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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
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