Synthesis, biological activity evaluation and mechanism of action of novel bis-isatin derivatives as potential anti-liver cancer agents

Zhifen Li, Jingbo Ma, Ming Tian, Peng Xia, Xiannian Lv, Rui Hou, Yuke Jiang, Xiaolong Xu, Zhifang Jia, Jigang Wang, Zhijie Li

Research output: Contribution to journalArticlepeer-review

Abstract

A series of bis-isatin conjugates with lysine linker were synthesized with the aim of probing their antiproliferative potential. All the newly synthesized derivatives (0–100 μM) were first screened against liver cancer cell lines(Huh1, H22, Huh7, Hepa1-6, HepG2, Huh6 and 97H) using CCK-8 assay. Results indicated that the derivative 4d exhibited the most potent activity against Huh1 (IC50 = 17.13 µM) and Huh7(IC50 = 8.265 µM). In vivo anti-tumor study showed that compound 4d effectively inhibited tumor growth in Huh1-induced xenograft mouse model; the anti-tumor effect of compound 4d (15 mg/kg) was comparable with sorafenib (20 mg/kg). H&E staining analysis and routine blood test and blood serum biochemistry examination was performed to confirm the safety of compound 4d in xenograft models. The mechanism of action of 4d on tumor growth inhibition was further investigated by RNA-Seq analysis, which indicates a positive regulation of autophagy signaling pathway, which was further confirmed with key biomarker expression of autophagy after 4d treatment. Our results suggest that the bis-isatin conjugate compound 4d is a promising tumor inhibitory agent for some liver cancer.

Original languageEnglish
Article number129613
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume99
Early online dateJan 2024
DOIs
Publication statusPublished - 1 Feb 2024

Fingerprint

Dive into the research topics of 'Synthesis, biological activity evaluation and mechanism of action of novel bis-isatin derivatives as potential anti-liver cancer agents'. Together they form a unique fingerprint.

Cite this