Silver salts of carboxylic acid terminated generation 1 poly (propyl ether imine) (PETIM) dendron and dendrimers as antimicrobial agents against S. aureus and MRSA

Abstract

Novel therapeutic strategies are essential to address the current global antimicrobial resistance crisis.Branched molecules with multiple peripheral functionalities, known as dendrimers, have gained interest as antimicrobials and have varying levels of toxicity. Silver displays activity against several microorganisms only in its positively charged form. In this study, silver salts of generation 1 (G1) poly (propyl ether imine) (PETIM) dendron and dendrimers were synthesised and evaluated for their antimicrobial potential against sensitive and resistant bacteria. The purpose was to exploit the multiple peripheral functionalities of G1 PETIM dendron and dendrimers for the formation of silver salts containing multiple silver ions in a single molecule for enhanced antimicrobial activity at the lowest possible concentration.G1 PETIM dendron, dendrimers and their silver salts were synthesised and characterised by FT-IR, 1 H NMR and 13 C NMR. PETIM silver salts were evaluated against Hep G2, SKBR-3 and HT-29 cell lines for their cytotoxicity using the MTT assay. The G1 PETIM dendron/dendrimers, silver nitrate and silver salts of the G1 dendron (compound 13), G1 dendrimer with an aromatic core (compound 14) and an oxygen core (compound 15) were evaluated for activity against S. aureus and methicillin-resistant S. aureus (MRSA) by the broth dilution method. PETIM silver salts were found to be non-cytotoxic even up to 100 mg ml À1 . Minimum inhibitory concentration values of compounds 13, 14 and 15 against S. aureus were 52.1, 41.7 and 20.8 mg ml À1 while against MRSA they were 125.0, 26.0 and 62.5 mg ml À1 , respectively. The calculated fractional inhibitory concentration index further indicated that compound 14 specifically displayed additive effects against S. aureus and synergism against MRSA. The enhanced antimicrobial activities of the PETIM dendron/dendrimer-silver salts against both sensitive and resistant bacterial strains widen the pool of available pharmaceutical materials for optimizing treatment of bacterial infections.

Inhibitory effects of fluoroquinolone antibiotics on <em>Babesia divergens</em> and <em>Babesia microti</em>, blood parasites of veterinary and zoonotic importance

“…Combination therapies of highly effective fluoroquinolone antibiotics (enrofloxacin, enoxacin, and trovafloxacin) with DA, luteolin, or PYR were tested on the in vitro cultures of B. divergens . Fluoroquinolone antibiotics/DA, luteolin, or PYR combinations (M1, M2, M3, and M4, respectively) were prepared as previously described 11 , 12 with some modifications. Combinations were based on the calculated IC 50 values obtained from the in vitro BFA ( Table S1 ).…”

Anti–Methicillin-Resistant Staphylococcus aureus Nanoantibiotics

“…Balogh reported polyamidoamine (PAMAM) dendrimer–silver complexes that have strong antimicrobial activity against various Gram-positive bacteria through a slow release of silver ions (Balogh et al, 2001). Poly(propyl ether imine) (PETIM) silver complexes have a better bioavailability compared with PAMAM and were found to be non-cytotoxic even at concentrations that would exhibit activity against S. aureus and MRSA (Jain et al, 2010; Suleman et al, 2015). Dendrimers containing quaternary ammonium salts as functional end groups exert antimicrobial behavior by disrupting bacterial membranes (Xue et al, 2015).…”

Novel dendritic derivatives of unsaturated fatty acids as promising transdermal permeation enhancers for tenofovir

“…77 MTT assay. The derivatives (PA1E 2, LA1E 3, LLA1E 4 and AA1E 5) were dissolved in DMSO and distilled water as a stock solution, and further diluted in the culture medium to give final concentrations of 20, 40, 60, 80 and 100 mg ml À1 .…”