Design, Synthesis, and Biological Evaluation of Naphthalimide-Polyamine Conjugate as a Potential Anti-Colorectal Cancer Agent.

Colorectal cancer is the second most common cause of cancer-related death worldwide, with a rising incidence, highlighting an urgent need for novel therapeutics. In this study, we developed several polyamine conjugates. Compound 6 (C6) was selected as the lead compound and was evaluated for anticancer activity in vitro and in vivo. In vitro experiments showed that C6 inhibited cell proliferation, colony formation, migration, and invasion of colorectal cancer cells while inducing apoptosis, pyroptosis, and autophagosome formation. Genetic or pharmacological inhibition of autophagy weakened C6-induced apoptosis and gasdermin E (GSDME)-dependent pyroptosis. Inactivation of caspase 3 activity by AC-DEVD-CHO decreased the levels of N-terminal GSDME induced by C6. Furthermore, animal models exhibited suppressed tumor growth and dissemination after treatment with C6. Taken together, our findings highlight C6 as a potential drug against colorectal cancer.