Punicalagin, a pomegranate polyphenol sensitizes the activity of antibiotics against three MDR pathogens of the Enterobacteriaceae.

BACKGROUND: Multidrug resistance (MDR) in the family Enterobacteriaceae is a perniciously increasing threat to global health security. The discovery of new antimicrobials having the reversing drug resistance potential may contribute to augment and revive the antibiotic arsenal in hand. This study aimed to explore the anti-Enterobacteriaceae capability of bioactive polyphenols from Punica granatum (P. granatum) and their co-action with antibiotics against clinical isolates of Enterobacteriaceae predominantly prevalent in South Asian countries. METHODS: The Kandhari P. granatum (Pakistani origin) extracts were tested for anti-Enterobacteriaceae activity by agar well diffusion assay against MDR Salmonella enterica serovar Typhi, serovar Typhimurium and Escherichia coli. Predominant compounds of active extract were determined by mass spectrometry and screened for bioactivity by agar well diffusion and minimum inhibitory concentration (MIC) assay. The active punicalagin was further evaluated at sub-inhibitory concentrations (SICs) for coactivity with nine conventional antimicrobials using a disc diffusion assay followed by time-kill experiments that proceeded with SICs of punicalagin and antimicrobials. RESULTS: Among all P. granatum crude extracts, pomegranate peel methanol extract showed the largest inhibition zones of 25, 22 and 19 mm, and the MICs as 3.9, 7.8 and 7.8 mg/mL for S. typhi, S. typhimurium and E. coli, respectively. Punicalagin and ellagic acid were determined as predominant compounds by mass spectrometry. In plate assay, punicalagin (10 mg/mL) was active with hazy inhibition zones of 17, 14, and 13 mm against S. typhi, S. typhimurium and E. coli, respectively. However, in broth dilution assay punicalagin showed no MIC up to 10 mg/mL. The SICs 30 µg, 100 µg, and 500 µg of punicalagin combined with antimicrobials i.e., aminoglycoside, ß-lactam, and fluoroquinolone act in synergy against MDR strains with % increase in inhibition zone values varying from 3.4 ± 2.7% to 73.8 ± 8.4%. In time-kill curves, a significant decrease in cell density was observed with the SICs of antimicrobials/punicalagin (0.03-60 µg/mL/30, 100, 500 µg/mL of punicalagin) combinations. CONCLUSIONS: The P. granatum peel methanol extract exhibited antimicrobial activity against MDR Enterobacteriaceae pathogens. Punicalagin, the bacteriostatic flavonoid act as a concentration-dependent sensitizing agent for antimicrobials against Enterobacteriaceae. Our findings for the therapeutic punicalagin-antimicrobial combination prompt further evaluation of punicalagin as a potent activator for drugs, which otherwise remain less or inactive against MDR strains.

Development of amylopectin based polyurethanes for sustained drug release studies.

In this research work, the crosslinked structure of polyurethane has been exploited for sustained drug delivery. Polyurethane composites have been prepared by the reaction of isophorone diisocyanate (IPDI) and polycaprolactone diol (PCL), which were further extended by varying the mole ratios of amylopectin (AMP) and 1,4-butane diol (1,4-BDO) chain extenders. The progress and completion of the reaction of polyurethane (PU) were confirmed using Fourier Transform infrared (FTIR) and nuclear magnetic resonance (1H NMR) spectroscopic techniques. Gel permeation chromatography (GPC) analysis showed that the molecular weights of prepared polymers were increased with the addition of amylopectin into the PU matrix. The molecular weight of AS-4 (Mw ≈ 99,367) was found threefold as compared to amylopectin-free PU (Mw ≈ 37,968). Thermal degradation analysis was done using thermal gravimetric analysis (TGA) and inferred that AS-5 showed stability up to 600 °C which was the maximum among all PUs because AMP has a large number of -OH units for linking with prepolymer resulting in a more cross-linked structure which improved the thermal stability of the AS-5 sample. The samples prepared with AMP showed less drug release (<53 %) as compared to the PU sample prepared without AMP (AS-1).

Tuning the optoelectronic properties of oligothienyl silane derivatives and their photovoltaic properties.

Four new Donor-Acceptor (D-A) type oligothiophenes based structures (C1-C4) were designed by substituting different acceptors moieties around tetrahedral silicon core to simulate their photovoltaic properties. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) quantum analysis were carried out to reconnoiter various parameters of solar cells. A comparative analysis has conducted between designed structures and reference molecule R to conclude our simulated results. Among all the structures, C2 has displayed highest absorption values (380 nm) with red shift and minimum band gap (ΔH-L) of 4.11 eV in dichloromethane at DFT-CAM-B3LYP/6-31G (d,p) using IEFPCM model. The C2 has also shown the lowest values of electron reorganization energy (λe = 0.018eV) and hole reorganization energy (λh = 0.015eV) therefore, could be suggested for use in organic solar cells because of its most noteworthy charge carrier mobilities. Again, C2 has the different trend in TDM graph because the electron density is present in the lower right part of core unit and in the acceptor moiety due to high electron affinities of end capped acceptor having cyanide groups.

Evaluation of cytotoxicity, hemocompatibility and spectral studies of chitosan assisted polyurethanes prepared with various diisocyanates.

In this research work cytocompatibility, mutagenicity, and hemolytic activity of chitosan-based polyurethanes (PUs) have been evaluated. The chitosan modified PUs were prepared by step-growth polymerization technique using various diisocyanates like isophorone diisocyanate (IPDI). 4,4'-methylenedicyclohexyl diisocyanate (H12MDI), 2,4-toluene diisocyanate (TDI) and hexamethylene diisocyanate (HMDI) by reacting with hydroxyl-terminated polybutadiene (HTPB). Structural confirmation of prepared samples was done by FTIR-ATR and 1H NMR techniques. Chitosan bearing PU samples showed good hemocompatibility, non-mutagenic behavior and less or non-cytotoxic behavior with all the diisocyanates. Among all the diisocyanates, aromatic diisocyanate (TDI) showed less hemocompatibility, high mutagenicity, and more cytotoxicity. However, this still showed a better result than non-chitosan based sample. It is concluded that chitosan improved the biological behavior of PU samples.

Mathematical modeling and experimental study of mechanical properties of chitosan based polyurethanes: Effect of diisocyanate nature by mixture design approach.

This research work has been done to investigate the influence of the geometry of aliphatic diisocyanate (hexamethylene diisocyanate, HDI), cycloaliphatic diisocyanate (isophorone diisocyanate, IPDI) and aromatic diisocyanate (2,4-toluene diisocyanate, TDI) on the tensile strength and hardness of chitosan based polyurethane biomaterials. For this purpose, chitosan (CS) and polycaprolactone diol (PCL) based polyurethanes have been synthesized with above mentioned diisocyanates following statistical design (mixture design). Simplex mixture design was used for analysis and totally 10 experiments were generated by the software. Samples were tested based on the portions of mixture components. Fourier transform Infrared attenuated total reflection (FTIR-ATR) and nuclear magnetic resonance (NMR) spectroscopic techniques confirmed the synthesis of chitosan based polyurethanes. This biomaterial has been established as an innovative and promising strategy to improve the mechanical strength of chitosan-based polyurethanes.