Antimicrobial Activity of a Series of 1-Alkyl-2-(4-Pyridyl)Pyridinium Bromides against Gram-Positive and Gram-Negative Bacteria

Abstract

Objective: To test a series of 1-alkyl-2-(4-pyridyl)pyridinium bromides with alkyl chains containing between 9 and 16 carbons against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia, Acinetobacter baumannii and Pseudomonas aeruginosa) bacteria. Materials and Methods: Chemical synthesis was based on the reaction of 2,4′-bipyridyl with alkyl bromide. Antimicrobial activity of the bipyridyls was measured by growing bacterial cultures on Mueller-Hinton agar in the presence and absence of inhibitors. Results:The compounds were most active against S. aureus. The most active compounds had alkyl chain lengths of between 11 and 16 carbons. Methicillin-sensitive S. aureus was more susceptible to the inhibitors than methicillin-resistant S. aureus (MRSA). Two subclasses of MRSA existed which differed in their susceptibility to the inhibitors. The susceptibility of MRSA strains to the compounds was increased in the presence of the efflux pump inhibitor reserpine. The activity of the compounds against Gram-negative organisms was increased when the membrane-permeabilizing agent sodium citrate was introduced. Critical micelle concentrations of the compounds were much higher than minimum inhibitory concentrations of the inhibitors. Conclusion: The mechanism of action of the compounds may involve perturbing bacterial membranes. The resistance of some MRSA strains to the compounds may be related to efflux pumps.

In Vitro Antibacterial Activity of 4-Phenyl-1-(2-phenyl-allyl)pyridinium bromide: A Novel Class of Pyridinium Based Antibacterial Compounds

“…These results are commonly reported as the MIC, which is defined as the lowest concentration of drug that inhibits the growth of the organism [13]. S. aureus is a highly pathogenic bacteria and responsible for number of diseases.…”

“…Interestingly among all the standard antibiotic tested, 4-phenyl-1-(2-phenyl-allyl)pyridinium bromide was the compound that could show antibacterial effect at very low concentration 20 lg/ml (Table 1). It showed high efficacy towards medically important S. aureus and it is a one of the bacterial strain that rapidly growing resistant towards antibiotics which are use to cure S. aureus infections [11,13]. More than 90% of S. aureus strains contain plasmids that encode beta lactamase, the enzyme that degrade many, but not all, penicillins.…”

“…More than 90% of S. aureus strains contain plasmids that encode beta lactamase, the enzyme that degrade many, but not all, penicillins. Some strains of S. aureus are resistant to the beta lactamase resistant penicillins, such as methicillin and [11,13,14].…”

“…Reagents and solvents used in the synthesis were obtained from various commercial sources with the highest purity available and did not subject to further purification. 1 H and 13 C NMR spectra of the final product were recorded on a Varian Oxford NMR YH 300 MHz spectrometer, and mass spectrum was obtained from Varian 310-MS TQ Mass Spectrometer (Varian, USA) with electron spray ionization (ESI). Melting point was uncorrected and determined using STUART scientific melting point apparatuses.…”

1-Alkyl-(N,N-dimethylamino)pyridinium bromides: inhibitory effect on virulence factors of Candida albicans and on the growth of bacterial pathogens

“…In addition, these drugs are often toxic to the host tissues. These circumstances warrant the development of new antimicrobials with high efficacy, low toxicity, a wide spectrum of activity and low costs and that are eco-friendly in nature (Denny et al, 2005;Ng et al, 2006;Rajeshkumar & Sundararaman, 2012).…”