Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality for cancer treatment, in which delivery agents containing 10B atoms are transported into tumor cells and then irradiated with low-energy (0.025 eV) thermal neutrons. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in the remodeling and degradation of all components of the extracellular matrix (ECM). MMP enzymes play a key role in normal development, morphogenesis, bone remodeling and angiogenesis yet overexpressed levels of MMP activity have been implicated in several disease states including tumor growth and metastasis. To date, about 24 mammalian MMPs have been identified, with specific therapeutic interest in MMP-1, MMP-2, MMP-9, and MMP-13 due to their overexpression in cancer. In order to halt disease progression resulting from exaggerated matrix remodeling mediated by MMPs, MMP inhibitors (MMPi) have been extensively explored as promising antitumor targets due to their selectivity and tight binding to different MMPs. We have appended a borane-rich carborane cluster onto MMP-targeting pharmacophores to enable delivery of 10B atoms to a tumor. The design, synthesis and molecular docking experiments of first series of BNCT ligands based on α-sulfone hydroxamate MMP inhibitor, SC-78080, were recently reported. Herein, we report the synthesis and molecular docking results of the synthesis of series of BNCT ligands based on the broad-spectrum MMP inhibitor, CGS-27023A

Synthesis of carborane-containing Matrix metalloproteinase (MMP) ligands as candidates for boron neutron capture therapy

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.