Design and synthesis of carborane-based antitubercular agents

Abstract

Tuberculosis (TB) is one of the leading causes of death globally, with 1.4 million people succumbing to the disease in 2021 alone. Current treatments for TB consist of extended drug regimens associated with moderate toxicity leading to undesirable side-effects. The demand of these treatment regimens on patients often leads to poor compliance, and in turn, the emergence of drug resistant strains. Consequently, there exists an urgent need for the development of new antibacterial agents with different modes of action to curb the increasing threat posed by the spread of infection, and the proliferation of resistance. This study explores the use of boron clusters to develop and assess a novel series of antitubercular agents with potent activity against the H37Rv strain of Mycobacterium tuberculosis (Mtb), the causative agent of TB. Dicarba-closo-dodecaboranes, more commonly referred to as carboranes, are a class of boron clusters which offer unique physical and chemical properties that are currently underutilised in drug development.

This thesis reports the development of a range of novel boron-based agents that inhibit Mtb with high potency. The carborane conjugates discussed demonstrate the potential of boron chemistry to broaden and enrich the design of new therapeutics, and deliver physiochemical advantages over traditional, solely organic scaffolds.