New 1,7-closo-carboranylanilinoquinazoline hybrids have been identified as EGFR inhibitors, one of them with higher affinity than the parent compound erlotinib. The comparative docking analysis with compounds bearing bioisoster-substructures, demonstrated the relevance of the 3D aromatic-boron-rich moiety for interacting into the EGFR ATP binding region. The capability to accumulate in glioma cells, the ability to cross the blood-brain barrier and the stability on simulated biological conditions, render these molecules as lead compounds for further structural modifications to obtain dual action drugs to treat glioblastoma.

The reported new anilinoquinazoline-icosahedral borane hybrids have been evaluated as glioma targeting for potential use in cancer therapy. Their anti-glioma activity depends on hybrids' lipophilicity; the most powerful compound against glioma cells, a 1,7-closo-derivative, displayed at least 3.3 times higher activity than the parent drug erlotinib. According to the cytotoxic effects on normal glia cells, the hybrids were selective for epidermal growth factor receptor (EGFR)-overexpressed tumor cells. These boron carriers could be used to enrich glioma cancer cells with boron for cancer therapy.

About 95 %o fp eopled iagnosed with glioblastoma die within five years. Glioblastoma is the mosta ggressivec entraln ervous systemt umour.I ti sn ecessary to make progress in the glioblastoma treatments ot hat advanced chemotherapy drugs or radiationt herapy or,i deally,t wo-in-one hybrid systems should be implemented.T yrosine kinase receptors-inhibitors and boron neutron capture therapy (BNCT), together,c ould provide at herapeutic strategy. In this work,s unitinibdecorated-carborane hybrids were prepared and biologically evaluatedi dentifying excellent antitumoral-and BNCT-agents. One of the selected hybrids was studieda gainst glioma-cells and found to be 4times more cytotoxic than sunitinib and 1.7 times more effectivet han 10 B-boronophenylalanine fructose complex when the cells were irradiated with neutrons.