Supplementary Information Raw Data File

We hypothesise that antimicrobial resistance (AMR) cannot be overcome by simply 'drugging' a single biological target, therefore, our focus is developing broad-spectrum therapeutics.Herein we present the synthesis of two novel spacer-linked, anthraquinone-triphenylphosphonium (AQ-TPP) conjugates (4) and (5) as early lead compounds in a new class of agent designed to penetrate the lipophilic barriers of the membranes of a diverse family of species; and establish bacterial growth inhibitory properties against methicillin-resistant <i>Staphylococcus aureus</i> (NCTC 13616) and Mycobacterium smegmatis [mc2155] (as a surrogate for <i>Mycobacterium tuberculosis</i>).The MIC and MBC values of (4) and (5) were determined against MRSA and found to be equipotent [MIC for each: 1 µg/mL (1.2 µM)]. Whereas the amide-linked conjugate (5) was determined to have 2-fold greater bactericidal potency [MBC 1 µg/mL (1.2 µM] than ester-linked (4).The anthraquinone-TPP conjugates (4) and (5) were active in vitro against <i>Mycobacterium smegmatis</i> and were equipotent as determined by their MIC values; in contrast to MRSA, the less hydrophobic (4) had 2-fold greater bactericidal potency than (5) as measured by their MBC values. Notably, both conjugates showed potent intracellular growth inhibitory activity in infected THP-1 macrophages. The conjugates are promising leads for the development of new antibacterial drugs.