Exploring diarylheptanoid derivatives to target LIMK1 as potential agents against colorectal cancer

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.