Synthesis, structural features and cytotoxicity of new calix[4]resorcinols with methanesulfonate fragments

Acid-catalyzed condensation of resorcinol, 2-methylresorcinol, and pyrogallol with 2-(4-formylphenoxy)ethyl methanesulfonate in a CHCl₃/CF₃CO₂H or MeOH/HCl_conc medium led to new rccc and rctt calix[4]resorcinol diastereomers bearing methanesulfonate fragments in high yields, with diasteromeric ratio depending on the nature of the solvent and acid used, as well as their proportions. The obtained compounds can be easily O-alkylated with propargyl bromide, and the subsequent click reaction with BnN₃ afforded new multi-functionalized triazole-containing derivatives. Screening against some cancerous and normal cell lines revealed a leading compound, rccc pyrogallol derivative, which exhibited cytotoxic activity against M-HeLa cancer cells at the level of the reference drug Sorafenib.