ABSTRACT
Maleimide-conjugating closo-dodecaborate sodium form 5c (MID) synthesized by the nucleophilic ring-opening reaction of closo-dodecaborate-1,4-dioxane complex 2 with tetrabutylammonium (TBA) azide was found to conjugate to free SH of cysteine and lysine residues in BSA under physiological conditions, forming highly boronated BSA that showed high and selective accumulation in tumor and significant tumor growth inhibition in colon 26 tumor-bearing mice subjected to thermal neutron irradiation.
Subject(s)
Boron Compounds/chemistry , Boron Neutron Capture Therapy/methods , Boron/administration & dosage , Maleimides/chemistry , Neoplasms/radiotherapy , Serum Albumin, Bovine/chemistry , Animals , Boron/therapeutic use , Cell Line , Cysteine/chemistry , Drug Carriers/chemistry , Female , Lysine/chemistry , Mice , Mice, Inbred BALB C , Models, MolecularABSTRACT
Diaryl-substituted ortho-carboranes 1 were synthesized from the corresponding alkynes by decaborane coupling under microwave-irradiated conditions with a combination of N,N-dimethylaniline and chlorobenzene. Among the compounds synthesized, 1a and 1d exhibited significant inhibition of hypoxia-induced HIF-1 transcriptional activity. Both compounds similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting HIF-1α mRNA expression.
