Calixarenes in a Membrane Environment:  A Monolayer Study on the Miscibility of Threep-tert-Butylcalix[4]arene β-Lactam Derivatives with 1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine

Abstract

Literature data indicate that some calixarene derivatives with antimicrobial activities may be useful as drugs; one of the aspects of the biological activity of different classes of antibiotics concerns interactions with lipid membranes. Here, the possibility of incorporation and/or translocation of three amphiphilic p-tert-butylcalix[4]arene derivatives across membranes was studied using lipid monolayers. The derivatives used have 6-aminopenicillanic acid or benzylpenicillin moieties grafted in alternate positions at the calixarene lower rim; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), a model bacterial membrane lipid, was used to prepare the monolayers. The miscibility of calixarene-antibiotic conjugates with lipid films was studied using surface pressure and surface potential measurements, as well as Brewster angle microscopy. The results obtained show that the miscibility is significantly different for the 6-aminopenicillanic acid and the two benzylpenicillin derivatives. Molecular modeling allowed the assessment of the lowest energy conformations of the calixarene derivatives and gave more insight into the interactions with the DMPE films.

Miscibility behavior of two-component monolayers at the air–water interface: Perfluorocarboxylic acids and DMPE

“…On the other hand, DMPE monolayers have the phase transition from a liquid-expanded (LE) to liquid-condensed (LC) phase at $12 mN m À1 (0.57 nm 2 , indicated by a dashed arrow) and the collapse pressure of $51 mN m À1 (0.37 nm 2 ). The data coincide with those reported previously [39][40][41].…”

Calix[4]arene based 1,3,4-oxadiazole and thiadiazole derivatives: Design, synthesis, and biological evaluation

“…[19][20][21] Regnouf and coworkers, focusing on the development of calixarene platforms designed molecular drug dispensers offering penicillin and quinolone moieties at the lower rim. [22][23][24][25] Ionic calixarene derivatives exhibit intrinsic antimicrobial activity, [26][27][28][29] while p-guanidino ethyl calixarene and parent phenol derivatives exhibited antibacterial activities. 30 Hydroxycinnamic acid based derivatives also had been reported as radical scavenging agents having antioxidant activity.…”

Antimicrobial Activity of Calixarenes and Related Macrocycles

“…The β-lactams' carboxylic acids were protected as pivavoyloxymethyl esters and reacted with the calixarene diester to form diamide 1 [14]. Although antimicrobial data were not published, this route led the way to an analogue, 2, in which penicillin V was appended to the calixarene [15] and tested against Gram-positive and Gram-negative bacteria [16]. The group also prepared a nalidixic acid delivering prodrug, 3.…”