The copper (II) ion as a carrier for the antibiotic capreomycin against Mycobacterium tuberculosis

Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus

“…This has been described for the copper homeostasis protein multicopper oxidase (CueO), which is inhibited by silver ions (53). Copper can also function as a carrier to increase the uptake of compounds across membranes, as proposed by Manning et al (18), but the exact opposite scenario in which the compounds serve as the carrier for copper ions is also conceivable and exemplified by the potential catechol-mediated uptake of copper in E. coli (54). It is also known that the coordination of copper with a ligand can change its mode of interaction with bacterial membranes, affecting its bioactivity and bioavailability, as proposed for moxifloxacin (55).…”

“…Indeed, other modes of action by which copper influences the antibacterial efficacy of compounds are now being investigated. For example, Manning et al proposed a carrier function of copper ions for the antibiotic capreomycin (18), and select intracellular proteins have been identified as potential specific targets of some copper complexes. These targets include the isocitrate lyase from M. tuberculosis (19) as well as the succinate and NADH dehydrogenase of Neisseria gonorrhoeae (17).…”

Survival in amoeba—a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a “copper pathogenicity island”

“…Recently, Festa et al have published a novel approach that allows accumulation of copper in pathogen cells without activating its Cu-resistant mechanisms and significantly increases selectivity of the treatment (Festa et al 2014). In other strategies, Cu(II) ions have been either utilized as carriers for known antibiotics, allowing them to bypass existing efflux-mediated resistance to drugs (Manning et al 2014;Lopes et al 2013;Shams et al 2014), or as chelators that upon binding to a ligand, change its conformation to the Bactive^mode (Haeili et al 2014). Several potent copper chelators with activity against MRSA and Mycobacterium tuberculosis strains have been identified through drug screening assays specifically designed for identification of copper-dependent antimicrobial compounds (Speer et al 2013) with, potentially, more discoveries on the way.…”

The effect of complexation of 3-formylrifamycin SV macrocyclic ether derivatives with metal cations and small nitrogen-containing organic molecules on antibacterial activity against S. aureus and S. epidermidis

“…2a). Differences in d C (15) indicate slightly changed conformation and an involvement of the amide group in the C(15)@OÁ Á ÁH-N(38) H-bonds within 1 and 9. However, a comparison of the 1 H NMR spectra of 9 and 1 shows no N + (38)H signals in the 7.5-9 ppm range in the former, while the positions of O(1)-H and O(4)-H proton signals are comparable in both recorded spectra (Fig.…”

“…14 In contrast, the same research group has found that the use of Capreomycin as a mixture with Cu 2+ and PEG showed some impact on the antibiotic efficiency against different bacteria strains. 15 Furthermore, it is well known that rifampicin (one of the 3-formyl rifamycin SV derivatives) spontaneously forms complexes with various metal cations with different coordination modes. 16 Recently we have synthesized several crown-ether derivatives of 3-formyl rifamycin SV which are potentially able to coordinate different species as, for example, metal cations.…”