GG-8-6, cyclo-(Val-Leu-Pro-Ile-Leu-Leu-Leu-Val-Leu, compound 1), and its twelve analogues (compound 2–13) were synthesized based on the lead compound Grifficyclocin B, a cyclic peptide with anti-tumor activity which was isolated from the plants of Goniothalamus species (Annonaceae). The bioassay results showed that these synthetic cyclopeptides exhibited different extent of cytotoxicity against human hepatocellular carcinoma cell lines. Among them, GG-8-6 (1) was the most active compound with IC₅₀ values of 6.38 μM and 12.22 μM against SMMC-7721 and HepG2, respectively. Further studies on the mechanism demonstrated that GG-8-6 (1) could induce apoptosis and G2/M arrest of HCC cells, and the activation of caspase pathways was probably involved. In vivo anti-tumor experiments showed that GG-8-6 (1) could significantly inhibit the growth of tumor in the mouse xenograft tumor model. At the dose of 40 mg/kg, the inhibition ratio was 67.9% without weight loss. Our results suggested that GG-8-6 (1), a new cyclic peptide, might be a potential candidate for developing new anti-HCC drug in the coming future.

GG-8-6，环- （VAL-LEU-PRO-ILE-LEU-LEU-LEU-VAL-LEU，化合物1），和它的12个类似物（化合物2 - 13）的合成根据先导化合物Grifficyclocin乙，是一种具有抗肿瘤活性的环状肽，是从Goniothalamus物种（Annonaceae）的植物中分离出来的。生物测定结果表明，这些合成的环肽对人肝癌细胞系表现出不同程度的细胞毒性。其中，GG-8-6（1）是活性最高的化合物，其对SMMC-7721和HepG2的IC ₅₀值分别为6.38μM和12.22μM。对该机理的进一步研究表明，GG-8-6（1）可能诱导HCC细胞凋亡和G2 / M阻滞，并且可能参与了caspase途径的激活。体内抗肿瘤实验表明，GG-8-6（1）可以在小鼠异种移植肿瘤模型中显着抑制肿瘤的生长。在40mg / kg的剂量下，抑制率为67.9％，没有重量减轻。我们的研究结果表明，新的环状肽GG-8-6（1）在未来的发展中可能是开发新的抗HCC药物的潜在候选者。