Scientists from the Zelinsky Institute have synthesized photostable analogs of combretastatin A4 with antiproliferative activity

A number of medications are very sensitive to light and are subjected to significant photodegradation. As a result, there is a decrease in the quality of the active substance, which leads to the loss of the effectiveness of the therapy used and to the formation of by-products that can be toxic. For these reasons, the considerable attention of scientists is currently paid to the issue of photostability of drugs: the mechanisms of photodegradation, pharmacokinetics of photoproducts, factors affecting photodegradation, as well as the possibility of increasing the photostability of the active substance of potential drugs are studied.

Over the past years, researchers at the Laboratory of Heterocyclic Compounds of the ZIOC have been developing biologically active compounds and light-sensitive materials based on combretastatin A4 derivatives, a drug that is actively used to treat cancer. Scientists investigated photochemical properties and antiproliferative activity of previously synthesized structures and it was found that despite promising biological characteristics, substances were subjected to significant photodegrdation with the loss of bioactivity under the influence of both UV and sunlight. In one of their latest works, taking into account the available results, the researchers carried out the design and targeted synthesis of new combretastatin A4 derivatives with improved photostability and high antiproliferative activity. The proposed structures can be obtained from available starting compounds in high yields.

Source:

Alexander Scherbakov, Alexey V. Zakharov, Ekaterina I. Mikhaevich, Diana I. Salnikova, Anton V. Yadykov, Arina A. Kozhevnikova, Valerii Z. Shirinian Photostability and Antiproliferative Activity of Furan Analogues of Combretastatin A‑4 // Chem. Res. Toxicol., 2022, accepted manuscript. DOI: 10.1021/acs.chemrestox.2c00204.