NOVEL CURCUMINOID-INSPIRED SYNTHETIC COMPOUNDS AS ANTI-TUMOR AGENTS

摘要

Novel CUR- and CUR-BF₂ compounds as well as novel bis and mono-NSAID/CUR-BF₂ and NSAID/CUR hybrids exhibiting anti-tumor properties are presented. CUR compounds bearing fluorinated moieties with selective fluorine introduction into the α-carbonyl moiety as well as CUR-BF₂ adducts and CURs with diverse substitution patterns in the phenyl rings including fluorinated substituents (SCF₃, OCF₃, and F) and/or bulky activating groups (OMe, OAc, and OBz) are presented. Fluorinated aryl-pyrazoles and isoxazoles as well as novel CUR and CUR-BF₂ compounds with monocyclic aromatic and bicyclic-heteroaromatic lateral rings, bearing fluorine(s), OCF₃, CF₃, and SCF₃ groups, and their alpha-carbonyl-fluorinated analogs, as well as their pyrazole and isoxazole derivatives are presented. The CUR-pyrazoles embody analogs that are fluorinated at the phenyl-pyrazole moiety. The hybrids, compounds, and their derivatives exhibited exceptional cytotoxic and anti-proliferative activity against several cancer cell-lines. The hybrid NSAID/CUR compounds also exhibited exceptional anti-inflammatory activity over NSAID or curcumin alone.