Novel terpestacin derivatives with l-amino acid residue as anticancer agents against U87MG-derived glioblastoma stem cells

Shengrong Liao; Nayeong Yuk; Yu Jin Kim; Huayan Xu; Xiaolin Li; Ling Wang; Yonghong Liu; Hye Jin Jung

doi:10.1016/j.bioorg.2023.106392

Novel terpestacin derivatives with l-amino acid residue as anticancer agents against U87MG-derived glioblastoma stem cells

Bioorg Chem. 2023 Mar:132:106392. doi: 10.1016/j.bioorg.2023.106392. Epub 2023 Jan 24.

Authors

Shengrong Liao¹, Nayeong Yuk², Yu Jin Kim², Huayan Xu³, Xiaolin Li⁴, Ling Wang⁵, Yonghong Liu⁶, Hye Jin Jung⁷

Affiliations

¹ CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: srliao@scsio.ac.cn.
² Department of Pharmaceutical Engineering and Biotechnology, Genome-Based BioIT Convergence Institute, Sun Moon University, Asan 31460, Korea.
³ Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁴ CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, Joint International Research Laboratory of Synthetic Biology and Medicine, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
⁶ CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yonghongliu@scsio.ac.cn.
⁷ Department of Pharmaceutical Engineering and Biotechnology, Genome-Based BioIT Convergence Institute, Sun Moon University, Asan 31460, Korea. Electronic address: poka96@sunmoon.ac.kr.

PMID: 36709667
DOI: 10.1016/j.bioorg.2023.106392

Abstract

Based on the natural product terpestacin, seventeen derivatives (1-17) with various l-amino acid side chains were designed and synthesized. Their anticancer activities against U87MG-derived glioblastoma stem cells (GSCs) were evaluated, and compounds 5, 11, 13 and 15 showed strong abilities to inhibit the proliferation (IC₅₀ = 2.8-6.9 μM) and tumorsphere formation of GSCs. Besides, compounds 13 and 15 could effectively induce apoptosis and significantly inhibit the invasion of GSCs (95 and 97 % inhibition, respectively, at 2.5 μM). The levels of CD133 marker in GSCs also decreased in dose-dependent manners after the treatment of these active compounds. Compared to terpestacin and the positive control A1938, our derivatives showed stronger activities and compounds 13 and 15 are promising candidates for further development as anticancer agents by targeting GSCs.

Keywords: Anticancer; Brain cancer; Glioblastoma stem cells; Terpestacin; l-amino acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / pharmacology
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Glioblastoma* / drug therapy
Humans
Neoplastic Stem Cells

Substances

Amino Acids
terpestacin
Antineoplastic Agents