Design and Synthesis of Metronidazole-Based Photoswitches With Potential Biological Applications

Photocontrol of the activity of biomolecules is a promising field to selectively target specific cells or tissues. Herein, we present a rational design of novel photoactive molecules which combine a metronidazole-like moiety, responsible for the cytotoxic activity, and a photoswitchable unit. The proposed compounds stand out for their straightforward synthesis (two steps through a simple and versatile route), as well as their photochemical and thermal stability. These compounds are water soluble and their photoisomerization takes place with a high quantum yield. A computational study was performed to guide the design of this novel family, to fully characterize their structure and properties and to aid in the analysis of the experimental results. Moreover, the photoisomerized forms feature cytotoxicity in the micromolar range against human cancer cell lines, allowing a complete off/on photocontrol of the biological activity.