Multifaceted Supramolecular Interactions from C‐Methylresorcin[4]arene Lead to an Enhancement in In Vitro Antibacterial Activity of Gatifloxacin

Abstract

Mimicking the antibacterial activity of polyphenols in synthetic systems is an attractive approach for the development of new active pharmaceutical ingredients. Resorcinarenes represent a class of polyphenols, which have been exploited for decades for their attractive chemical scaffold suitable for forming host-guest complexes with hydrophobic guest molecules. However, the polyphenolic character of resorcinarenes, which could be a potential asset to the pharmaceutical industry, have been least exploited. The present work represents an unprecedented interplay of antimicrobial activity of resorcinarene together with its ability to interact chemically with an antibacterial drug gatifloxacin, improving the overall antibacterial activity. The chemistry and the clinical activities involved in this study were investigated simultaneously by spectroscopic techniques, as well as by in vitro measurement of antibacterial activity toward two human bacterial pathogens, a Gram-positive pathogen Staphylococcus aureus and a Gram-negative lung pathogen Legionella pneumophila. The initial positive result obtained from this study could revolutionize the use of synthetically modifiable resorcinarenes and their analogues in fine tuning the clinical behavior of drugs.

Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application

“…Unarguably, all the tested materials can potentially qualify for direct use in clinical events as drug carriers or drug modifiers. This result is particularly encouraging considering that at least one of these compounds (RsC1) has already demonstrated in vitro anti-bacterial activity (25). Therefore, investigations of a library of calixarene-based synthetic compounds and their innumerable derivatives, including metallosupra-molecular assemblies, should be considered in connection with the development of new drugs and drug carriers.…”

“…The structural similarities between the calixarene family and polyphenols recently encouraged us to assess the role of Cmethylresorcin [4]arene (RsC1) in conjunction with the anti-bacterial drug gatifloxacin. To our surprise, RsC1 by itself exhibited a significantly low MIC 90 value against a Gramnegative lung pathogen, Legionella pneumophila, showing its merit for consideration as a future drug candidate (25). In contrast, a supramolecular complex of RsC1 with gatifloxacin exhibited superior behaviour when compared with the drug alone by improving the MIC 90 value against a Gram-positive pathogen, Staphylococcus aureus.…”

Antimicrobial Activity of Calixarenes and Related Macrocycles

“…aureus and the human lung pathogen Legionella pneumophila subsp. pneumophila ATCC 33152 [82]. The complex had a lower MIC against S. aureus than the antibiotic alone, 0.16 µg mL −1 against 0.195 µg mL −1 , whereas with L. pneumophila, an MIC of 0.025 µg mL −1 was found whether the drug was complexed or not.…”

“…aureus and the human lung pathogen Legionella pneumophila subsp. pneumophila ATCC 33152 [82]. The complex had Calix [4]resorcinarenes were also used by Kashapov and colleagues [80].…”

Supramolecular Antibacterial Materials for Combatting Antibiotic Resistance

“…Using a similar strategy, Kumari and co‐workers constructed a supramolecular bacteriostatic complex consisting of C‐alkylresorcin[4]arene (RsC1) and the antibacterial drug gatifloxacin, formed through synergistic acid/base, hydrogen‐bonding, and charge‐transfer interactions . The antibiotic‐based supramolecular complex also exhibits significantly lower MIC values against Gram‐negative pathogens compared to those of commercial gatifloxacin.…”