Trace and destroy
A new luminous molecule analog of an American drug will help diagnose and treat cancer
RNF Press Service
Kazan scientists have synthesized complex molecules that can be used to treat cancer and monitor the process of targeted delivery to the body, which will significantly improve the results of therapy. In addition, the development will allow creating high-quality and cheap analogues of foreign drugs. The results of the study, supported by a grant from the Presidential Program of the Russian Science Foundation (RNF), are published in the journal Pharmaceuticals (Akhmedov et al., Fluorescein-Labelled Thiacalixarenas as Potential Theranostic Molecules: Synthesis, Self-Association, and Antitumor Activity).
More recently, 19.3 million new cases of cancer and almost 10 million deaths from it were registered in the world; according to experts, in 2040 the number of new cases will reach 28.4 million. An important role in the development of a tumor is played by the fact that cancerous, that is, incorrectly functioning and uncontrollably dividing cells "escape" from attacks from the immune system. This happens because neoplasms create special protection around themselves. One of the defenders is galectin, which is involved in all stages of tumor formation — from the germination of blood vessels into it to the increase of the neoplasm in size. In this regard, galectin inhibitors are often used as modern anticancer drugs — substances that suppress the activity of this molecule.
Researchers Kazan Federal University (Kazan) synthesized thiacalixarene, a cyclic structure consisting of four aromatic fragments combined into one large molecule. These macrocycles are an analogue of the tumor growth inhibitor — anginex. Interestingly, antitumor drugs based on it have already been obtained and patented in the USA. The method proposed in the article will allow synthesizing more affordable and cheaper analogues in Russia.
"Our work is based on the idea of combining a drug and a fluorescent marker in one molecule to create a multifunctional drug. It is able to provide both therapy of malignant neoplasms and monitoring of drug bio—distribution in the body," says the first author of the article Alan Akhmedov, Candidate of Chemical Sciences, junior researcher at the Laboratory for the Study of organic Compounds of KFU.
To prove the effectiveness of the compounds obtained, scientists conducted experiments on artificially grown cultures of lung cancer, as well as duodenal cancer, since it is these types of tumors that actively produce galectin, against which the action of macrocycle molecules is directed. It turned out that the substances successfully suppressed tumor growth in both cases. It also turned out that the strength of the interaction of the macrocycle with tumor cells is influenced by its size and conformation — the arrangement of atoms in the molecule. Thus, the compounds in the "cone" conformation interacted better with tumor cells and destroyed them. This is due to the fact that they had more available amino groups (–NH2), which increase the chances of drug interaction with galectin.
"Macrocycles penetrate both living and dead cancer cells and are potential antitumor molecules. In addition, the fluorescent fragment in the proposed compounds will allow controlling the delivery and distribution of drugs in the human body. In the future, we plan to conduct additional preclinical and clinical experiments," says Pavel Padnya, PhD in Chemistry, Senior researcher at the Laboratory for the Study of Organic Compounds of KFU, the head of the project supported by a grant from the Russian Academy of Sciences.
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