Flow Synthesis of Nature-Inspired Mitochondria-Targeted Phenolic Derivatives as Potential Neuroprotective Agents

A series of phenolic derivatives designed to selectively target mitochondria were synthesized under flow conditions starting from natural phenolic acids. The two-step continuous flow protocol, performed in Cyrene, a bioavailable dipolar aprotic solvent, allowed the isolation of the MITO compounds in moderate to good yields. The MITO compounds obtained, as a first step, were tested for their safety by cell viability analysis. The cytocompatible dose, in human neuronal cell line SH-SH5Y, depends on the type of compound and the non-toxic dose is between 3.5 and 125 mu M. Among the seven MITO compounds synthesized, two of them have shown interesting performances, being able to protect mitochondria from oxidative insult.

Automated summary

A series of phenolic derivatives targeting mitochondria were synthesized under flow conditions starting from natural phenolic acids. The two-step continuous flow protocol in the bioavailable solvent Cyrene allowed for the isolation of the MITO compounds with moderate to good yields. The safety of the compounds was evaluated by cell viability analysis, and the non-toxic dose ranged from 3.5 to 125 μM in the human neuronal cell line SH-SH5Y. Two of the synthesized MITO compounds showed interesting performances in protecting mitochondria from oxidative damage.