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新型2-氯-3-(1-苯并咪唑-2-基)喹啉衍生物作为抗肿瘤剂的设计、合成及药理学评价：抗肿瘤活性、细胞周期阻滞及凋亡反应

Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1-benzo[]imidazol-2-yl)quinoline derivatives as antitumor agents: and antitumor activity, cell cycle arrest and apoptotic response.

作者信息

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

机构信息

School of Pharmacy, Guilin Medical University North Ring 2nd Road 109 Guilin 541004 PR China

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University Guilin 541004 PR China.

出版信息

RSC Adv. 2018 Jul 6;8(43):24376-24385. doi: 10.1039/c8ra04640a. eCollection 2018 Jul 2.

DOI:10.1039/c8ra04640a
PMID:35539175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9082043/
Abstract

A series of novel 2-chloro-3-(1-benzo[]imidazol-2-yl)quinoline derivatives (3a-3d) were designed and synthesized as antitumor agents. 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. antitumor assay results showed that the representative compound 3a exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model. Mechanistic studies suggested that 3a may exert antitumor activity by the up-regulation of Bax, intracellular Ca 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.

摘要

设计并合成了一系列新型的2-氯-3-(1-苯并咪唑-2-基)喹啉衍生物(3a - 3d)作为抗肿瘤剂。抗肿瘤试验结果表明，一些化合物对HepG2、SK-OV-3、NCI-H460和BEL-7404肿瘤细胞系表现出中度至高抑制活性，并且与5-氟尿嘧啶和顺铂相比，大多数化合物对HL-7702正常细胞系的细胞毒性要低得多。抗肿瘤试验结果表明，代表性化合物3a在HepG2异种移植小鼠模型中对肿瘤生长表现出有效的抑制作用。机制研究表明，3a可能通过上调Bax、细胞内钙释放、活性氧生成、p21、p27和p53，下调Bcl-2，激活caspase-9和caspase-3以及随后PARP的裂解，以及抑制CDK活性来发挥抗肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66af/9082043/f4e88e89779e/c8ra04640a-f10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66af/9082043/110b75be9e25/c8ra04640a-f6.jpg
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