Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma.

Abstract

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation.

• Authors: Chaochao Ge, Liping Chang, Ying Zhao, Congcong Chang, Xiaojuan Xu, Haoying He, Yuxia Wang, Fujun Dai, Songqiang Xie, Chaojie Wang
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 22 Issue 2 (Feb 22 2017) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 28241441 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cadherins
• Naphthalimides

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis
• Cadherins (metabolism)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Cycle
• Cell Line, Tumor
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Lung Neoplasms (drug therapy, secondary)
• Mice
• Molecular Structure
• Naphthalimides (chemical synthesis, pharmacology)