Hsueh-Yun Lee

This study synthesized a series of C2 and N 1‐substituted benzimidazole hydroxamic acid ( 6 ‐ 19 ) as HDAC inhibitors. Among them, most of 2‐aryl(alkyl)benzimidazole hydroxamic acids ( 11 ‐ 16 ) exhibited HDAC6 activity and slight HDAC1 (or HDAC2) activity. In addition, they also showed anti‐angiogenic activity and inhibited the growth of tested cancer cells. For instance, compound 13 has a GI ₅₀ of 3.9 μM against EPCs and inhibited the growth of HCT‐116, SK‐Hep‐1, and PC‐3 cells with GI ₅₀ values of 1.3, 4.2, and 7.5 μM, respectively. The exact mechanism underlying the anti‐angiogenic effects of these compounds remains unknown, though this study gives an insight into how future HDAC inhibitors that aim to target blood vessel formation can be designed.

The K ₂ S ₂ O ₈ -mediated generation of p -iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione.

Correction for ‘CuI-mediated synthesis of 1-aryl-5,6,7-trimethoxybenzimidazoles as potent antitubulin agents’ by Cong-Min Peng et al., RSC Adv., 2023, 13, 13169–13176, https://doi.org/10.1039/D3RA01927F.

In situ CuI-mediated cyclization helps construct N-aryl-5,6,7-trimethoxybenzimidazoles. Compound 10 displayed potent antiproliferative activity and inhibitory activity of tubulin polymerization.

Inhibiting a specific target in cancer cells and reducing unwanted side effects has become a promising strategy in pancreatic cancer treatment. MAP4K4 is associated with pancreatic cancer development and correlates with poor clinical outcomes. By phosphorylating MKK4, proteins associated with cell apoptosis and survival are translated. Therefore, inhibiting MAP4K4 activity in pancreatic tumours is a new therapeutic strategy. Herein, we performed a structure-based virtual screening to identify MAP4K4 inhibitors and discovered the compound F389-0746 with a potent inhibition (IC₅₀ 120.7 nM). The results of kinase profiling revealed that F389-0746 was highly selective to MAP4K4 and less likely to cause side effects. Results of in vitro experiments showed that F389-0746 significantly suppressed cancer cell growth and viability. Results of in vivo experiments showed that F389-0746 displayed comparable tumour growth inhibition with the group treated with gemcitabine. These findings suggest that F389-0746 has promising potential to be further developed as a novel pancreatic cancer treatment. Graphical abstract