Enzymatic synthesis of poly(catechin)-antibiotic conjugates: an antimicrobial approach for indwelling catheters

Abstract

Biofilm formation in urinary indwelling catheters is one of the most critical issues that patients face. Catheters were coated with poly(catechin)-antibiotic conjugates with enhanced antimicrobial properties. Catechin was conjugated with two antibiotics, namely trimethoprim (TMP) and sulfamethoxazole (SMZ) via activation with N,N'-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing α-amine moieties. Silicone and polyurethane catheters were functionalized in situ through laccase oxidation of catechin-antibiotic conjugates. Four antimicrobial coatings were produced, namely with poly(catechin), poly(catechin)-TMP, poly(catechin)-SMZ and poly(catechin)-TMP-SMZ. The bacterial adhesion reduction was tested on the functionalized devices using gram-negative and gram-positive strains. The most significant reduction in adhesion was observed with poly(catechin)-TMP (gram-negative -85 % and gram-positive -87 %) and with poly(catechin)-TMP-SMZ (gram-negative -85 % and gram-positive -91 %). The cytotoxicity to mammalian cells was tested by indirect contact for 5 days and revealed that all the tested coatings supported more than 90 % of viable cells. A promising approach for the increase of the indwelling catheter lifespan was developed aiming to reduce catheter-associated chronic infections.

Antimicrobial lubricant formulations containing poly(hydroxybenzene)-trimethoprim conjugates synthesized by tyrosinase

“…4 Bacterial reduction (%) of S. epidermidis and E. coli when exposed to polyphenolic lubricant formulations. Four samples were tested: (1) lubricant-containing poly(hydroxybenzene) resulted from methylparaben oxidation by tyrosinase, (2) lubricant-containing poly(catechin) resulted from catechin oxidation by laccase, (3) lubricant-containing poly(hydroxybenzene)-trimethoprim conjugates obtained by in situ enzymatic oxidation of methylparaben and trimethoprim using tyrosinase, and (4) lubricant-containing poly(catechin)-trimethoprim conjugates produced in two operational steps as described by Gonçalves et al (2015). Each assay was performed at 37°C for 24, 48, and 72 h cosmetic, and pharmaceutical products (Beheshti et al 2008;Velickova et al 2009).…”

“…Moreover, these highly hydroxylated compounds have great biological activities such as anti-inflammatory, anti-allergic, anti-thrombosis, antioxidant, and antimicrobial properties (Alberto et al 2011). As described previously by Gonçalves et al (Gonçalves et al 2015), the conjugation of polyphenols with antibiotics had a synergistic effect against bacterial growth. The oxidation process involved a two-stage method in which the monomer (catechin) was chemically conjugated with antibiotics and further polymerized through laccase action.…”

“…In situ enzymatic synthesis of poly(catechin)-trimethoprim conjugates through laccase action According to Gonçalves et al (2015), the enzymatic synthesis of poly(catechin)-trimethoprim conjugates followed a twostep pathway: (1) chemical conjugation of catechin with trimethoprim and (2) enzymatic polymerization of catechintrimethoprim conjugates through laccase oxidation. In the first stage, the conjugation was initiated by the activation of hydroxyl groups present at the catechin structure by mixing 0.03 M of phenol with DSC (0.1 M) and DMAP (0.1 M) in 1,4-dioxane anhydrous under a nitrogen atmosphere for 24 h. Subsequently, for catechin-trimethoprim conjugation, 1 eq.…”

“…As previously mentioned, the two-step enzymatic synthesis of poly(catechin)-trimethoprim via laccase oxidation reported by Gonçalves et al (2015) was also assessed in this work aiming to compare the antimicrobial efficiency of two polyphenolantibiotic conjugates. When polyphenolic-trimethoprim conjugates were added into the lubricant formulation, the main difference macroscopically observed was the color change.…”

“…Herein, the poly(hydroxybenzene)-trimethoprim conjugates were produced through in situ enzymatic oxidation of methylparaben using tyrosinase as biocatalyst. The poly(catechin)-trimethoprim conjugates were obtained following the Gonçalves et al (2015) methodology. Both polyphenolic-antibiotic conjugates were incorporated into a newly optimized lubricant matrix envisaging a topical application and the antimicrobial activity of each formulation was evaluated against gram-negative and gram-positive bacteria.…”