Di-anionic self-associating supramolecular amphiphiles (SSAs) as antimicrobial agents against MRSA andEscherichia coli

Abstract

Amphiphilic agents demonstrate selective antimicrobial activity against MRSA and are shown to form interesting macrocyclic structures in the solid state.

Tools to enable the study and translation of supramolecular amphiphiles

“…24. 11,15,34,36,37,41,47,48,181,182 This extensive systematic approach combines multiple complimentary characterisation techniques in the solution- and solid-state, as well as in the gas-phase. Using this approach enables a comprehensive data set to be collected describing both the physiological and physicochemical properties of supramolecular amphiphiles.…”

Supramolecular Self-Associating Amphiphiles Inhibit Biofilm Formation by the Critical Pathogens, Pseudomonas aeruginosa and Candida albicans

“…Traditionally, a limitation to the translation of amphiphilic agent technologies, such as SSAs, into the clinic is demonstration of enhanced hemolysis activity levels against erythrocytes (red blood cells). To assess the implication of SSA hemolysis activity on SSA clinical potential, we have determined the hemolytic activity for several SSAs, including 1 . In addition, we have also conducted in vivo mouse model studies, in which 3 and 9 were introduced into mice intravenously; the SSA concentration within the mouse circulatory system (alongside SSA dissemination into lung, muscle, and liver tissue) was then recorded with respect to time .…”

Establishing the selective phospholipid membrane coordination, permeation and lysis properties for a series of ‘druggable’ supramolecular self-associating antimicrobial amphiphiles

“…To date, these SSAs, 14 of which are included in Fig. 1, have been shown to: (i) exhibit antimicrobial efficacy against both clinically relevant Gram-positive methicillin resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli); [26][27][28][29] (ii) have the potential to act as drug delivery vehicles; 27,30 (iii) enhance the activity of octenidine, ampicillin and cisplatin against E. coli and novobiocin and rifampicin against Pseudomonas aeruginosa; 31,32 and (iv) enhance the activity of the anticancer agent cisplatin against ovarian cancer cells. 33 We have previously hypothesised that SSA therapeutic activity is related to the ability of these agents to selectively coordinate with and permeate membranes of differing phospholipid composition.…”