Design & Synthesis of Novel Nitrofuranyl Indole Carboxylates as Potential Antibacterial Drug Conjugates

Abstract

Mankind has immensely benefited from the first marketed antibacterial drug i.e. Salvarsan® in 1910 to the recently released Vaborem®, and the discovery of penicillin gave birth to the modern age of antibacterial treatment. Since the ‘golden age’ of antibacterial discovery (from the ‘40s to the ‘60s), in which most common antibacterial agents were discovered, antibacterial discovery has slowed dramatically with no new antibacterial scaffolds being introduced from 1962 until 2000. Recent developments in Oxford have led to identification of non-β-lactam indole carboxylates as potent metallo-β-lactamase inhibitors; as a result, and in extension of the aforementioned endeavours in combating antibacterial resistance, herein this work reports a set of novel nitrofuranyl indole carboxylates (NInCs) which are thought to have potential to be developed into antibacterial drug conjugates. Inasmuch as stable ester prodrugs of the aforementioned NInCs may be biologically inactive, this work also presents various methods for ester hydrolysis of these potential antibacterial drug conjugates together with some modification to their cleavable linkers.