calixarenes and Bacterial-Infections

β-lactam antibiotics are among the most important and widely used antimicrobials worldwide and are comprised of a large family of compounds, obtained by chemical modifications of the common scaffolds. Usually these modifications include the addition of active groups, but less frequently, molecules were synthesized in which either two β-lactam rings were joined to create a single bifunctional compound, or the azetidinone ring was joined to another antibiotic scaffold or another molecule with a different activity, in order to create a molecule bearing two different pharmacophoric functions. In this review, we report some examples of these derivatives, highlighting their biological properties and discussing how this strategy can lead to the development of innovative antibiotics that can represent either novel weapons against the rampant increase of antimicrobial resistance, or molecules with a broader spectrum of action.

Topics: Animals; Anti-Bacterial Agents; Azetidines; Bacteria; Bacterial Infections; beta-Lactams; Calixarenes; Drug Discovery; Humans; Lactams, Macrocyclic

The treatment of pathogenic bacterial infection has long been the most serious threat to human life and attracted widespread attention. Herein, a supramolecular photosensitizer platform based on carboxylatopillar[5]arene (CP5) and tetrafluorophenyl porphyrin functionalized with a quaternary ammonium group (TFPP-QA) for combating bacteria and dispersing biofilm via photodynamic treatment is constructed. By introducing the host macrocycle CP5 and host-guest interaction, the supramolecular photosensitizer has great biocompatibility and acid responsiveness. On the one hand, the acid-triggered dissociation of TFPP-QA/CP5 could induce the porphyrin photosensitizer to target bacterial cells and disrupt the charge balance of bacterial membranes, enhance the permeability of the bacterial membrane. On the other hand, the TFPP-QA/CP5 antibacterial platform possesses superb reactive oxygen species (ROS) generation capability under light irradiation, leading to enhanced photodynamic antibacterial efficacy. The in vitro and in vivo studies show that the supramolecular photosensitizers exhibit high antibacterial efficiency and biofilm dissipation effect under 660 nm light irradiation. Therefore, it is anticipated that the rational design and integration of photosensitizers and quaternary ammonium compounds through the supramolecular strategy would provide a promising prospect for clinical photodynamic antimicrobial therapy.

Topics: Bacterial Infections; Biofilms; Calixarenes; Humans; Photochemotherapy; Photosensitizing Agents; Porphyrins; Quaternary Ammonium Compounds

Two well-known antibiotic heterocycles, the 'quinolone' nalidixic acid and the β-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether-ester junction to the p-tert-butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dis-symmetrical podand incorporating one penicillin and one nalidixic ester moieties.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Calixarenes; Humans; Microbial Sensitivity Tests; Nalidixic Acid; Penicillin V; Staphylococcus aureus