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Synthesis

Light-Triggered Chemotherapy

Medicinal Chemistry: Chemists aim to curb side effects of chemotherapy with small molecules that isomerize from an inactive form to an active one in the presence of blue light

by Bethany Halford
July 13, 2015 | A version of this story appeared in Volume 93, Issue 28

Although many small-molecule drugs target cancer cells’ microtubules, these compounds often work at a patient’s peril. That’s because they don’t distinguish between microtubules of cancer cells and healthy cells, resulting in serious side effects. Chemists have now come up with a strategy to target tumor cells selectively by using compounds that switch from an inactive form to an active conformation when exposed to light (Cell 2015, DOI: 10.1016/j.cell.2015.06.049). Dirk Trauner and Oliver Thorn-Seshold, of Ludwig Maximilian University, in Munich, spearheaded the development of the compounds, known as photostatins, or PSTs. PSTs’ structures are based on that of the natural product combretastatin A-4. The researchers replaced the natural product’s cis C=C with N=N so that it can be photoisomerized easily and reversibly with low-intensity visible light. In the presence of blue light, the PSTs adopt the active cis conformation. In the dark or in the presence of green light, the molecules switch to the trans form. Cell culture experiments show the cis form is 250 times as cytotoxic as the trans form. To treat patients, the researchers envision using light-equipped bandages for cancerous skin lesions and implantable light-emitting diodes for tumors within the body.

Reaction scheme shows how blue and green light convert PST-1 between its cis and trans forms.

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