Phosphorylated derivatives of 1,3-azoles, their synthesis, physicochemical properties, antitumor and antibacterial activity. The aim of the study was to obtain new phosphorylated 1,3-azole derivatives, establish relationships between their structure, electronic characteristics and biological activity, and assess their potential as promising antitumor and antibacterial agents.
The research involved methods of organic synthesis, purification and structural characterization of the obtained compounds using IR spectroscopy, 1H, 13C and 31P NMR spectroscopy, mass spectrometry and elemental analysis. Antitumor activity was evaluated in vitro using the NCI-60 cancer cell line panel and selected tumor cell lines with determination of GI50, TGI, LC50 and IC50 values. Antibacterial activity was studied by serial dilution methods with determination of minimum inhibitory and bactericidal concentrations. Molecular docking, quantum-chemical calculations, QSAR and ADMET modelling were used to predict possible mechanisms of action, pharmacokinetic parameters and structure–activity relationships.
A series of phosphorylated 1,3-oxazole and 1,3-thiazole derivatives bearing different substituents at the C(2), C(4) and C(5) positions was synthesized. The influence of the nature of the azole ring, phosphorylated fragment and sulfur-containing substituents on biological activity was established. It was shown that selected phosphonium salts and phosphonate derivatives exhibit pronounced antitumor activity, including activity against melanoma, breast cancer and leukemia cell lines. Some phosphonium salts demonstrated combined antitumor and antibacterial properties, in particular against clinical isolates of Acinetobacter baumannii.
The scientific novelty of the study lies in the targeted synthesis of new phosphorylated 1,3-azole derivatives and the establishment of structure–activity relationships for these series. The role of sulfur oxidation state, electronic characteristics and the nature of the phosphorus-containing fragment in the manifestation of biological activity was determined. The obtained experimental and in silico data provide a basis for further rational design of biologically active phosphorylated heterocycles.
The results have been published in scientific journals and presented at international and national conferences. They may be used in further research aimed at the development of new potential antitumor and antibacterial agents, as well as in teaching organic, medicinal and bioorganic chemistry. Field of application: bioorganic chemistry, organic chemistry and medicinal chemistry.
