Design, synthesis and antibacterial evaluation of a polycationic calix[4]arene derivative alone and in combination with antibiotics.

The growing antibiotic resistance phenomenon continues to stimulate the search for new compounds and strategies to combat bacterial infections. In this study, we designed and synthesized a new polycationic macrocyclic compound (2) bearing four N-methyldiethanol ammonium groups clustered and circularly organized by a calix[4]arene scaffold. The in vitro activity of compound 2, alone and in combination with known antibiotics (ofloxacin, chloramphenicol or tetracycline), was assessed against strains of Staphylococcus aureus (ATCC 6538 and methicillin-resistant isolate 15), S. epidermidis (ATCC 35984 and methicillin-resistant isolate 57), and Pseudomonas aeruginosa (ATCC 9027 and antibiotic-resistant isolate 1). Calix[4]arene derivative 2 showed significant antibacterial activity against ATCC and methicillin-resistant Gram positive Staphylococci, improved the stability of tetracycline in water, and in combination with antibiotics enhanced the antibiotic efficacy against Gram negative P. aeruginosa by an additive effect.

Remarkable alkali cation template effect in 1,5-bridged calix[8]arenes.

Treatment of 1,5-bridged calix[8]arenes 2-4 with alkali metal carbonates produces salts in which an included cation acts as a conformational template. This induces the folding of calix[8]arene skeleton in a conformation in which the triads of contiguous OH-bearing rings adopt a 3/4-cone conformation with all hydroxyls converging toward the same center. The template effect requires the presence of short bridges (ethylene, tetramethylene, diethylene glycol) and became stronger by increasing the cation dimension up to that of Cs(+).