Objectives TNBG‐5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG‐5602 in in‐vitro and in‐vivo models and investigated its possible anticancer mechanism. Methods The antiproliferation effect of TNBG‐5602 in vitro was evaluated in human liver cancer cell line QGY‐7701. The acute toxicity of TNBG‐5602 was evaluated in mice. The anticancer activity of TNBG‐5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY‐7701. Key findings The results of CCK‐8 assay showed that TNBG‐5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG‐5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG‐5602 could remarkably inhibit the growth of tumours. During in‐vitro and in‐vivo studies, we noted that TNBG‐5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG‐5602 may be exerted through activating peroxisome proliferator‐activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA). Conclusions Our results suggested that TNBG‐5602 might exert potent anticancer activity through increasing the expression of PPARγ.

Tetrazanbigen (TNBG) is a novel sterol isoquinoline derivative with poor water solubility and moderate inhibitory effects on human cancer cell lines via lipoapoptosis induction. Herein, we developed a series of novel TNBG analogues with improved water solubility and antiproliferative activities. The CCK-8 assay enabled us to identify a novel compound, 14g, which strongly inhibited HepG2 and A549 cell growth with IC 50 values of 0.54 and 0.47 μM, respectively. The anticancer effects might be explained by the partial activation and upregulation of PPARγ expression, as indicated by the transactivation assay and western blotting evaluation. Furthermore, the in vitro antiproliferative activity was verified in an in vivo xenograft model in which 14g strongly reduced tumor growth at a dose of 10 mg/kg. In line with these positive observations, 14g exhibited an excellent water solubility of 31.4 mg/mL, which was more than 1000-fold higher than that of TNBG (4 μg/mL). Together, these results suggest that 14g is a promising anticancer therapeutic that deserves further investigation.