Synthesis and biological evaluation of closo-dodecaborate ibuprofen conjugate (DIC) as a new boron agent for neutron capture therapy

Authors:   Satomu Ishii,Hiroyuki Nakamura,
Journal: Journal of Organometallic Chemistry
https://doi.org/10.1016/j.jorganchem.2018.02.026
Abstract: A closo-dodecaborate ibuprofen conjugate (DIC) 1 was synthesized via amide bond formation between ibuprofen activated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) and 4-aminoethoxyethoxy-closo-dodecaborate 3 which was synthesized via the ring opening reaction of 1,4-dioxane-closo-dodecaborate complex 2 with ammonia in aqueous solution. DIC showed no significant binding affinity to HSA site 2, which is known as an ibuprofen binding site. DIC accumulated in HeLa cells in a time-dependent manner, and the boron concentration reached 0.68 μg/106 cells 6 h after administration.