Design, synthesis, and anticancer properties of isocorydine derivatives | |
Department | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Yan, Qian1,3; Li, Ruxia1,2; Xin, Aiyi1,3; Han, Yin1; Zhang YX(张燕霞)1; Liu JX(柳军玺)1; Li, Wenguang2; Di DL(邸多隆)1; Liu JX(柳军玺) | |
2017 | |
Source Publication | Bioorganic and Medicinal Chemistry |
ISSN | 0968-0896 |
Volume | 25Issue:24Pages:6542-6553 |
Abstract | Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 (24) was the most active with IC50 values under 10 μM (IC50 for HepG2 = 7.51 µM; IC50 for HeLa = 6.32 μM). FICD (12) and COM33 (24) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, β-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 (24) in vivo was 73.8% after a dose 100 mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 (24) (50 mg/kg) with sorafenib (50 mg/kg) was 66.5%. The results indicated that these isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC. |
Keyword | Isocorydine Aporphine Alkaloid Structure Modification Anticancer Activity Hepatocellular Carcinoma |
Subject Area | 分析化学与药物化学 |
DOI | 10.1016/j.bmc.2017.10.027 |
Funding Organization | the National Natural Science Foundation of China (NSFC No. 21672225) |
Indexed By | SCI |
Language | 英语 |
Funding Project | 药物工艺标准研究组 |
compositor | 第一作者单位 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.licp.cn/handle/362003/23805 |
Collection | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Corresponding Author | Liu JX(柳军玺) |
Affiliation | 1.CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, PR China 2.Gansu Key Laboratory of Preclinical Studies for New Drugs, Institute of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China 3.University of Chinese Academy of Sciences, Beijing 10049, PR China |
Recommended Citation GB/T 7714 | Yan, Qian,Li, Ruxia,Xin, Aiyi,et al. Design, synthesis, and anticancer properties of isocorydine derivatives[J]. Bioorganic and Medicinal Chemistry,2017,25(24):6542-6553. |
APA | Yan, Qian.,Li, Ruxia.,Xin, Aiyi.,Han, Yin.,Zhang YX.,...&柳军玺.(2017).Design, synthesis, and anticancer properties of isocorydine derivatives.Bioorganic and Medicinal Chemistry,25(24),6542-6553. |
MLA | Yan, Qian,et al."Design, synthesis, and anticancer properties of isocorydine derivatives".Bioorganic and Medicinal Chemistry 25.24(2017):6542-6553. |
Files in This Item: | ||||||
File Name/Size | DocType | Version | Access | License | ||
1-s2.0-S096808961731(2028KB) | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Application Full Text |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment