Synthesis and biological evaluation of bis-chalcone conjugates containing lysine linker as potential anticancer agents

Li, Zhifen1; Tian, Ming2,3,4; Ma, Jingbo2,3; Xia, Siyu2,3; Lv, Xiannian5; Xia, Peng4; Xu, Xiaolong2,3; Jiang, Yuke2,3; Wang, Jigang2,3,6,7; Li, Zhijie2,3

2023-09-15

10.1016/j.molstruc.2023.135785

JOURNAL OF MOLECULAR STRUCTURE   影响因子和分区

0022-2860

1872-8014

Eight bis-chalcone conjugates with lysine linker were synthesized by alkylation reaction and evaluated for the antiproliferative potential. All the newly synthesized derivatives were first screened against Liver cancer (MHCC-97H), Colorectal cancer (HCT116), and Gastric cancer (TMK1) using CCK-8 assay under the concentrations from 0 to 100 mu M, suggesting that gastric cancer cell TMK1 is more sensitive to these derivatives except 3d and 3f. Further, these compounds were tested in more gastric cancer-related cells including MKN45, AGS, IM95 and a normal gastric epithelial (GES1) cell line. Results indicated that the derivative 3a exhibited the most potent activity against TMK1 (IC50 = 22.29 mu M, near to the reference drug 5-FU) and AGS(IC50 = 22.14 mu M). In vivo anti-tumor study showed that compound 3a effectively inhibited tumor growth in TMK1-induced xenograft model without visible side effects. The mechanism of action on 3a on tumor growth inhibition was further investigated by RNA-Seq analysis in TMK1 cells, which indicates a positive regulation of apoptotic signaling pathway. Finally, cancer cell apoptosis after treated with 3a was confirmed with the expression of Annexin V, cleaved caspase 3 and Bax in TMK1 cells. Our results suggest that the bis-chalcone conjugate compound 3a is a promising tumor inhibitory agent for some gastric cancer.

Chalcone derivatives Cancer therapy Gastric cancer RNA-Seq

SCI

英语

通讯

Doctoral Scientific Research Foundation of Shanxi Datong University, Guangdong Basic and Applied Basic Research Foundation[2021A1515012164] ; International Science and Technology Cooperation for Shenzhen Technology Innovation Plan[GJHZ20200731095411034]

Chemistry

Chemistry, Physical

WOS:001010755900001

ELSEVIER

CHEMISTRY

Web of Science

1.Shanxi Datong Univ, Sch Chem & Chem Engn, Xing Yun St, Datong 037009, Shanxi, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Geriatr,Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Shenzhen Clin Re, Shenzhen 518020, Guangdong, Peoples R China
4.Wuhan Univ, Zhongnan Hosp, Dept Hepatobiliary & Pancreat Surg, Wuhan 430072, Hubei, Peoples R China
5.Fifth Peoples Hosp Datong City, Dept Geriatr, Shanxi Prov 2669 Wenxing Rd North, Datong 037006, Shanxi, Peoples R China
6.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
7.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

Li, Zhifen,Tian, Ming,Ma, Jingbo,et al. Synthesis and biological evaluation of bis-chalcone conjugates containing lysine linker as potential anticancer agents[J]. JOURNAL OF MOLECULAR STRUCTURE,2023,1288.

Li, Zhifen.,Tian, Ming.,Ma, Jingbo.,Xia, Siyu.,Lv, Xiannian.,...&Li, Zhijie.(2023).Synthesis and biological evaluation of bis-chalcone conjugates containing lysine linker as potential anticancer agents.JOURNAL OF MOLECULAR STRUCTURE,1288.

Li, Zhifen,et al."Synthesis and biological evaluation of bis-chalcone conjugates containing lysine linker as potential anticancer agents".JOURNAL OF MOLECULAR STRUCTURE 1288(2023).