New Dihalogenated Derivatives of Condensed Benzimidazole Diones Promotes Cancer Cell Death Through Regulating STAT3/HK2 Axis/Pathway

An effective method for synthesizing dihalogenated derivatives of condensed benzimidazole diones with a nodal nitrogen atom has been developed. As a result, five new heterocyclic quinones were obtained, which differed in the structure of the heterocycle annelated to imidazole, as well as the nature and arrangement of halogen atoms. A comprehensive analysis of the anticancer potential of new heterocyclic quinones revealed pronounced cytotoxic activity of the molecules against tumor cells. Using in silico methods for predicting activity spectra, it was found that the synthesized compounds are capable of interacting with a number of key targets that play an important role in oncogenesis, with the highest probability of binding to STAT3, the central regulator of cell growth, proliferation and metabolism. Experimental studies have shown that, despite the lack of pronounced ability to induce apoptosis, these substances effectively inhibit the activity of allosteric glycolytic enzymes, disrupting metabolic adaptation and energy balance of tumor cells. The obtained results expand the understanding of the molecular basis of the antitumor action of heterocyclic compounds and lay a solid foundation for their use as promising modulators of tumor cell metabolism.