The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• antibacterial agents. Keywords: NDH-2; phenothiazine; siderophore; siderophore–antibiotic; siderophore conjugate; Introduction One of the biggest challenges facing the modern society is antibiotic resistance and the prospect of current antibiotics becoming near redundant against previously treatable

• , the potency of such phenothiazines, including 1, needs to be significantly increased to have more activity in vivo and direct clinical application [11]. A validated target of 1 has been identified as type II NADH dehydrogenase (NDH-2), a respiratory enzyme essential for growth in M. tuberculosis and

• other bacterial species [11]. NDH-2 is absent in mammalian cells and similar to PBPs is associated with the bacterial membrane [12]. Considering the significant antibacterial activity of phenothiazines, in particular the anti-TB activity of 1, and their membrane-associated NDH-2 target we hypothesised 1