Synthesis of Novel Acetylene-Containing Phosphonates, Their Antiviral Activity, and Their Cytotoxicity to Different Cancer Cell Lines

This work focuses on rapid, catalyst-free synthesis of a new series of acetylenic phosphonates as promising building blocks for creating antiviral and anticancer agents. A comprehensive assessment of the biological activity of the synthesized compounds was conducted. Dialkyl phosphonates 4d, 4e, and 4g were found to exhibit pronounced antiproliferative activity against human cancer cell lines, with the greatest IC50 = 6 μg/mL against the K562 cell line. Further studies revealed that these compounds cause significant disorganization of the actin cytoskeleton, leading to the loss of stress fibers and reduced cell motility. In contrast, diamide derivatives demonstrated a more favorable safety profile, with low cytotoxicity and moderate antiviral activity against influenza A (H1N1) virus, among which compound 6b achieved a selectivity index of 5 with IC50 = 56.9 μg/mL. Screening studies of both dialkyl and diamide acetylenic phosphonates revealed some features of the interaction with kinase and nonkinase targets used for drug development and provide a basis for the subsequent rational design of novel selective anticancer agents based on the acetylenic phosphonate scaffold.