13-a

LIMK1 has been demonstrated to be highly correlated with the progression and overall survival rates of colorectal cancer (CRC) patients. In this study, a series of diarylheptanoid scaffold derivatives were intentionally designed and synthesised to evaluate their potential as LIMK1 inhibitors. Among these compounds, compounds 13a and XV exhibited LIMK1 inhibitory activity with IC₅₀ values of 0.94 and 0.57 µM, respectively. We also disclosed the structure-activity relationship of the resulting compounds that exhibited LIMK1 inhibition. Catechol-containing diarylheptanoid was identified as a promising scaffold for LIMK1 inhibitors. Notably, compound 13a demonstrated selectivity in inhibiting the tyrosine kinase-like family and exhibited potent inhibition of CRC cells. Moreover, compound 13a induced an increase in the S phase and a decrease in the G0/G1 phase in a dose-dependent manner, indicating apoptosis induction. These findings establish compound 13a as a lead compound for the further development of anti-CRC agents.