Scientists at the N.S. Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences have unveiled a novel approach to tackling drug resistance, focusing on targeting the internal mechanisms of cells rather than surface components. According to the authors, the approach can reduce the likelihood of resistance development against antibiotics, antitumor agents, and antiviral drugs.
The innovative strategy involves designing low-toxic inorganic and metal-complex compounds with a three-dimensional polyhedral structure. These molecules are capable of disrupting critical cellular processes by blocking allosteric enzyme centers and interfaces involved in macromolecular interactions.
Yan Voloshin, a corresponding member of the Russian Academy of Sciences and lead author of the research, explained that the rigid 3D bioeffectors can stereochemically “close” target regions, serving as universal molecular platforms. This structural design reduces the likelihood of resistance development. Furthermore, efforts will be made to identify and synthesize compounds that exhibit specific bioactivity, high selectivity for target biological systems, and low toxicity. The research, completed as a state assignment and supported by the Russian Ministry of Education and Science,
emphasizes the importance of the molecule’s shape, size, and topology—particularly the outer surface recognized by bioreceptors—over its chemical composition. This modular configuration allows for tailored compounds targeting various biosystems.
Unlike conventional small organic molecules that bind to surface sites and are vulnerable to mutation-induced resistance, the proposed compounds focus on allosteric sites and protein–protein interfaces. Their geometric rigidity reduces the risk of drug escape.
Potential applications include combatting resistant bacterial infections, cancer, viral diseases, and neurodegenerative conditions. Future efforts will expand the library of 3D compounds and refine their selectivity profiles, prioritizing low toxicity and precise targeting.
