Alkylation reactions of α-carboxylate phosphabetaines were carried out and studied to enhance the biological activity of previously synthesized carboxylate phosphabetaines. As a result of these reactions, the original structure was destroyed with the formation of quaternary salts of phosphonium triiodide. The structure and composition were confirmed by a complex of physical research methods, including NMR, IR spectroscopy, and elemental analysis. The bactericidal and antimycotic activity of the synthesized salts was assessed. The compounds showed activity similar to that of commercial drugs. The reactions of complexation of these structures were also investigated. In the reactions with nickel and copper chloride, complexes were isolated and characterized. The structure of the nickel complex was unambiguously confirmed by the data obtained with the help of single-crystal X-ray diffraction analysis.

As a result of reactions of nucleophilic addition of tertiary phosphines to pulegone in the presence of hydrochloric acid, quaternary phosphonium salts were obtained. Structure of the obtained compounds was established using a complex of spectral methods. Antibacterial and antifungal properties were determined for some phosphonium salts.

The acid-catalyzed reaction of 1,1-diethoxypropane derivatives with 2-naphthol, 2,7-naphthalenediol, and sesamol leads to the formation of new diarylmethanes and dibenzoxanthenes. The proposed method allows for the relatively facile introduction of the required functional group into the propylene fragment. Cytotoxic activity of all synthesized compounds was studied against normal and human cancer cell lines. Structures of the obtained compounds were confirmed by NMR (¹H, ³¹P, ¹³C) and single crystal X-ray diffraction analysis.

The convergence of ligand-based and structure-based computational strategies provides a robust foundation for hit optimization in anticancer drug discovery. We integrated ligand-based SAR with structure-based covalent docking to guide the optimization of haloacetamide-derived di(hetero)arylmethanes. SAR revealed that the 2-haloacetamide warhead is essential, while the di(hetero)aryl scaffold modulates activity, leading to submicromolar bis(pyrazolyl)methane hits. Rather than seeking to establish a definitive molecular target, we used GAPDH and GSTO1 as experimentally motivated target hypotheses to derive structural constraints for covalent scaffold design. Covalent docking was used to prioritize these hypotheses and guide the design of phosphorylated diarylmethane derivatives, leading to the identification of highly cytotoxic bromoacetamide compound, comparable to doxorubicin. In PANC-1 cells, this lead decreased LDH activity and increased PDH activity, suggesting a shift in cellular metabolism from glycolysis toward oxidative phosphorylation. The results demonstrate the utility of target-hypothesis-guided design under conditions in which molecular target identity remains unresolved.