Affiliation:
1. Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China
2. Center of Gerontology and Geriatrics, West China Hospital Sichuan University Chengdu China
Abstract
AbstractIn modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual‐target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS‐275. Among them, compound 24 (IC50 = 8.22 ± 0.27 μM) showed better anti‐tumor activity than the clinical Class I HDAC inhibitor MS‐275 (IC50 = 14.65 ± 0.24 μM) in MCF‐7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3–HDAC pathway inhibitor achieved with a single molecule.