Injectable antibacterial tissue-adhesive hydrogel based on biocompatible o-phthalaldehyde/amine crosslinking for efficient treatment of infected wounds.

Injectable antibacterial hydrogels have attracted considerable attention in wound management. However, the development of injectable hydrogels with excellent antibacterial activity, good biocompatibility, and strong tissue adhesion remains a challenge. In this study, an antibacterial tissue-adhesive hydrogel was developed based on a catalyst-free o-phthalaldehyde (OPA)/amine reaction by simply mixing OPA-terminated four-arm poly(ethylene glycol) (4aPEG-OPA) and ε-poly-l-lysine (ε-PLL) solutions. The hydrogel showed tunable gelation time, storage moduli, and degradation rate depending on the polymer concentration and 4aPEG-OPA/ε-PLL mass ratio. The hydrogel exhibited nearly 100% bacterial inhibition rates in-vitro against Gram-negative E. coli and Gram-positive S. aureus, while maintaining good biocompatibility. The hydrogel matched well in shape and tightly adhered to the tissue after in-situ formation at the wound sites. Following the treatment of rat models of full-thickness skin incisions and round wounds, the hydrogel effectively closed the wounds and promoted wound healing. Moreover, after administering to S. aureus infected full-thickness skin wounds, the hydrogel exhibited remarkable efficacy in inhibiting wound infection with a bacterial inhibition rate over 99.94%, achieving a significantly accelerated wound healing compared with the commercially available Prontosan® gel. Therefore, the hydrogel exhibits great potential as a wound dressing for infection prevention and promotion of healing.

Azacoccones F-H, new flavipin-derived alkaloids from an endophytic fungus Epicoccum nigrum MK214079.

Three new flavipin-derived alkaloids, azacoccones F-H (1-3), along with six known compounds (4-9) were isolated from the endophytic fungus Epicoccum nigrum MK214079 associated with leaves of Salix sp. The structures of the new compounds were established by analysis of their 1D/2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data. The absolute configuration of azacoccones F-H (1-3) was determined by comparison of experimental electronic circular dichroism (ECD) data with reported ones and biogenetic considerations. Epicocconigrone A (4), epipyrone A (5), and epicoccolide B (6) exhibited moderate antibacterial activity against Staphylococcus aureus ATCC 29213 with minimal inhibitory concentration (MIC) values ranging from 25 to 50 µM. Furthermore, epipyrone A (5) and epicoccamide A (7) displayed mild antifungal activity against Ustilago maydis AB33 with MIC values of 1.6 and 1.8 mM, respectively. Epicorazine A (8) showed pronounced cytotoxicity against the L5178Y mouse lymphoma cell line with an IC50 value of 1.3 µM.

Activity of Hospital Disinfectants against Vegetative Cells and Spores of Clostridioides difficile Embedded in Biofilms.

Clostridioides difficile spores can survive in the environment in either mono- or mixed-species biofilms. However, no previous studies have investigated chemical disinfection of C. difficile spores embedded in biofilms. Thus, the purpose of this study was to assess the in vitro effectiveness of hospital disinfectants against C. difficile spores embedded within biofilms. Five unique C. difficile strains embedded in three different biofilm types grown for 72 or 120 h were exposed to seven different hospital disinfectants. C. difficile abundance [as log(number of CFU/milliliter)] was calculated after manufacturer-determined contact times along with biofilm biomass and microscopy. The primary analysis compared differences between C. difficile vegetative cell and spore counts as well as amounts of biomass after exposure to disinfectants. C. difficile vegetative cells and spores were recovered from biofilms regardless of the type of biofilm growth or biofilm growth time. No disinfectant was able to completely eliminate C. difficile from the biofilms. Overall, Clorox, ortho-phthalaldehyde (OPA), and Virex were most effective at killing C. difficile spores regardless of biofilm age, ribotype, or wash conditions (whether biofilms are washed or unwashed) (P = 0.001, each). Clorox and OPA were also effective at killing total vegetative cell growth (P = 0.001, each), but Virex was found to be ineffective against vegetative cell growth in biofilms (P = 0.77). Clorox and Virex were most effective in reducing biomass, followed by Nixall, OPA, and Vital Oxide. No disinfectant was able to completely eliminate C. difficile embedded within biofilms although differences among disinfectants were noted. Future research will be required to determine methods to eradicate this persister reservoir.

Anticancer potential of NF-κB targeting apoptotic molecule "flavipin" isolated from endophytic Chaetomium globosum.

BACKGROUND: Anticancer compounds from natural sources have drawn attention due to their structural diversity and relatively lesser side effects. Endophytic fungi are one such natural resource from, which plethoras of anticancerous compounds have been isolated. PURPOSE: The objective of the study was to isolate and characterize the bioactive metabolite from Chaetomium globosum that exhibits astonishing antiproliferative activity against cancerous cell lines. METHODS: Flavipin was isolated by bioassay-guided fractionation and identified using FT-IR, EI-MS and NMR studies. MTT assay was used to determine the cytotoxicity. Fluorescent staining (AO/EB) and DNA fragmentation studies confirmed the occurrence of apoptosis. Real time PCR and Western blotting were used to analyze the expression of apoptosis related genes and its proteins, respectively. RESULTS: Flavipin inhibited proliferation of A549, HT-29 and MCF-7 cancer cells in dose dependent manner with an IC50 concentration of 9.89 µg/ml, 18 µg/ml and 54 µg/ml, respectively, whereas it was comparatively less sensitive (IC50 = 78.89 µg/ml) against normal cell line (CCD-18Co). At IC50 concentration cancerous cells exhibited cell shrinkage and fragmentation of DNA, which indicated that flavipin induced apoptotic cell death. In treated cells there is an up-regulation of p53 gene and its associated protein, whereas reciprocal expression was observed in BCL-2 gene and its protein. Furthermore, western blotting results also showed down-regulation of NFκB. CONCLUSION: This is the first report on the antiproliferative activity of flavipin isolated from endophytic C. globosum and also proposed that interaction of flavipin with NFкB could be a possible mechanism for this activity. Flavipin induced apoptosis at low concentrations in cancer cell lines (A549, HT-29) and exhibited itself as a potential anticancer agent.

Desinfectantes químicos de uso clínico: Aldehídos / No disponible

No disponible

Hydroxymethyl bioisosteres of phenolic GluN2B-selective NMDA receptor antagonists: Design, synthesis and pharmacological evaluation.

Antagonists addressing selectively NMDA receptors containing the GluN2B subunit are of particular interest for the treatment of various neurological disorders including neurodegenerative diseases. With the aim to bioisosterically replace the metabolically labile phenol of 7-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-ols, several analogs were docked into the ifenprodil binding site leading to the hydroxymethyl derivatives 4 as promising candidates. They display the same binding pose as Ro 25-6981 and the same H-bond interactions with Gln110 and Glu236 within the GluN2B subunit. The phenylalkyl moieties occupy the hydrophobic pocket formed predominantly by Pro78 (GluN2B), Phe114 (GluN2B), and Tyr109 (GluN1b). Starting from o-phthalaldehyde, the hydroxymethyl derivatives 4 were prepared in a 7-step synthesis with a haloform reaction of trichloroacetophenone 7 as key step. In receptor binding studies, the phenylpropyl derivative 4a shows promising GluN2B affinity (Ki = 101 nM) and high selectivity over the PCP binding site and both σ receptor subtypes. 4a was able to inhibit the glutamate/glycine induced cytotoxicity at mouse fibroblasts with an IC50 value of 5.2 µM. It is assumed that the hydroxymethyl moiety of 4a stabilizes the closed channel conformation by an H-bond with Glu236 as does the phenolic OH moiety of 3, Ro 25-6981 and ifenprodil.

An exception to the rule "no association between antibiotic resistance and decreased disinfectant microbicidal efficacy": Orthophthalaldehyde (OPA) and Pseudomonas aeruginosa isolated from ICU and paraplegic patients.

BACKGROUND: Antibiotic resistance and decreased susceptibility to disinfectants are not usually associated in microorganisms, but we have found an exception to this rule: P. aeruginosa versus orthophthalaldehyde (OPA). METHODS: Bactericidal effect of OPA was measured at 10 minutes on endodoncy files contaminated with an ATCC strain (control) or 206 strains of P. aeruginosa recently isolated from 206 ICU and paraplegic patients in a tertiary university hospital, in two consecutive years. RESULTS: Differences in bactericidal effect of OPA were found between the strains isolated each year (decreased susceptibility in the first period), but in both years the statistical differences (p < 0.05) were maintained according to whether the strains were "susceptible" to antibiotics, "resistant" (to one family of antibiotics) or "multi-resistant" (resistant to more than one family of antibiotics), exhibiting a reduction in their OPA susceptibility in parallel to an increase of their antibiotic resistance. In contrast, there were no differences depending on the type of sample (sputum, urine, faeces, pharynx) or of patient (paraplegic or ICU: adult, newborn, burn). Finally we selected 15 strains with an OPA effect below 3.5 log10 at 10 minutes and repeated the study with an OPA exposure of 15 minutes. In these conditions OPA showed a total bactericidal effect on these P. aeruginosa strains. CONCLUSIONS: There was an association between antibiotic resistance and decreased OPA susceptibility. This normally does not require an increase in disinfection time, but, for endoscope disinfection or instruments from colonized/infected patients with resistant/multiresistant P. aeruginosa, we consider it better to use 15 min of OPA. Regular tests (e.g., once every 12 months) with germ-carriers, should be performed to assess ecological changes in susceptibility to high level disinfectants and must include not only ATCC strains, but also recently isolated microorganisms with different antibiotic sensitivities (susceptible, resistant and multi-resistant).

Effects of immersion disinfection of agar-alginate combined impressions on the surface properties of stone casts.

This study investigated the effects of disinfection of agar-alginate combined impressions on the surface properties of the resulting stone casts. Two brands of cartridge-form agar impression material and one alginate impression material were used. Agar-alginate combined impressions of smooth glass plates were prepared. The impressions were immersed in 0.55% ortho-phthalaldehyde solution or 0.5% sodium hypochlorite solution for 1, 3, 5 and 10 min. A stone cast made with an impression that had not been immersed was prepared as a control. The surface roughness (Ra) of the stone casts was measured, and the cast surfaces were observed by SEM. Immersion of agar-alginate combined impressions in 0.5% sodium hypochlorite solution for up to 10 min had no serious adverse effects on the surface properties of the stone casts. In contrast, even 1 min of immersion in 0.55% ortho-phthalaldehyde solution caused deterioration of the cast surface properties.

Analysis of a panel of rapidly growing mycobacteria for resistance to aldehyde-based disinfectants.

After several accounts across the globe of mycobacteria outbreaks associated with medical procedures and aldehyde disinfectants resistance, we undertook an analysis of mycobacteria isolated from patients seen in a hospital in the United States between 1994 and 2008 to determine prevalence of resistance to aldehyde-based disinfectants. Out of the 117 clinical isolates screened, 6 isolates belonging to the emerging Mycobacterium abscessus group were found to display significant levels of resistance to glutaraldehyde and ortho-phthalaldehyde.

Synergistic sporicidal effect of ethanol on a combination of orthophthalaldehyde and didecyldimethylammonium chloride.

UNLABELLED: The objective of this study was to evaluate the potential synergistic effect of ethanol on a combination of orthophthalaldehyde (OPA) and didecyldimethylammonium chloride (DDAC) against the spores of Bacillus subtilis var. Niger. The quantitative carrier test for sporicidal testing of high-level disinfectants according to the guideline of China (Technical Standard for Disinfection 2002) was used as method. Considerable synergistic effect was observed after a 30-min treatment at 20°C. There was an augment in mean log reduction as the concentration of DDAC was increased ranging from 0·2 to 3 g l(-1) in combination with 6 g l(-1) OPA. Ten and 20% ethanol in combination with 6 g l(-1) OPA and 2 g l(-1) DDAC caused more than a 3-log reduction while either 6 g l(-1) OPA, 2 g l(-1) DDAC and 20% ethanol alone or a combination of two of the three agents produced less than a 1-log reduction. Further, 40-min exposure time of combination of OPA, DDAC and 20% ethanol led to greater than a 5-log reduction in spores, and no spore growth was observed following 60- and 90-min exposures. SIGNIFICANCE AND IMPACT OF THE STUDY: Orthophthalaldehyde (OPA) is very effective at concentrations far lower than its recommended in-use concentration of 0·5% (w/v) and is equally effective against both the gram-negative and gram-positive bacteria. However, it shows lower activity against spores. The synergistic sporicidal effect exhibited by ethanol on a combination of OPA and DDAC can be considered to enhance sporicidal activity for using in situations of sterilization, to reduce in-use concentration of OPA used alone, which may minimize its side effect. OPA may be a more satisfactory and the first-choice agent to replace glutaraldehyde (GTA) as a high-level disinfectant for medical devices.

Inhibitory activity of carbonyl compounds on alcoholic fermentation by Saccharomyces cerevisiae.

Aldehydes and acids play important roles in the fermentation inhibition of biomass hydrolysates. A series of carbonyl compounds (vanillin, syringaldehyde, 4-hydroxybenzaldehyde, pyrogallol aldehyde, and o-phthalaldehyde) were used to examine the quantitative structure-inhibitory activity relationship of carbonyl compounds on alcoholic fermentation, based on the glucose consumption rate and the final ethanol yield. It was observed that pyrogallol aldehyde and o-phthalaldehyde (5.0 mM) reduced the initial glucose consumption rate by 60 and 89%, respectively, and also decreased the final ethanol yield by 60 and 99%, respectively. Correlating the molecular descriptors to inhibition efficiency in yeast fermentation revealed a strong relationship between the energy of the lowest unoccupied molecular orbital (ELUMO) of aldehydes and their inhibitory efficiency in fermentation. On the other hand, vanillin, syringaldehyde, and 4-hydroxybenzaldehyde (5.0 mM) increased the final ethanol yields by 11, 4, and 1%, respectively. Addition of vanillin appeared to favor ethanol formation over glycerol formation and decreased the glycerol yield in yeast fermentation. Furthermore, alcohol dehydrogenase (ADH) activity dropped significantly from 3.85 to 2.72, 1.83, 0.46, and 0.11 U/mg at 6 h of fermentation at vanillin concentrations of 0, 2.5, 5.0, 10.0, and 25.0 mM correspondingly. In addition, fermentation inhibition by acetic acid and benzoic acid was pH-dependent. Addition of acetate, benzoate, and potassium chloride increased the glucose consumption rate, likely because the salts enhanced membrane permeability, thus increasing glucose consumption.

Disinfection of rigid nasal endoscopes following in vitro contamination with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae.

IMPORTANCE: If not adequately cleaned, rigid nasal endoscopes (RNEs) have the potential to cause iatrogenic cross-contamination. OBJECTIVE: To test the efficacy of various disinfection methods in reducing bacterial load on RNEs in vitro. DESIGN AND SETTING: In vitro model. INTERVENTIONS: Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae contamination was separately induced on RNEs in vitro. Two experimental sets were completed. The RNEs were disinfected using the following protocols: 30-second scrub with antimicrobial soap (ABS) and water, 30-second scrub with 70% isopropyl alcohol (IA), 30-second scrub with ABS followed by 30-second scrub with IA, 30-second scrub with germicidal cloth, isolated 5-minute soak in an enzymatic soap solution, 5- and 10-minute soaks in ortho-phthalaldehyde, 0.55%, solution (Cidex OPA), and isolated 30-second rinse with tap water, all with 30-second precleaning and postcleaning rinses with tap water. Two sets of experiments (experiment sets A and B) were carried out with a 30-second tap water rinse after inoculation of each RNE. This was followed by immediate cleaning in set A and a 1-hour air-dry delay in set B. Otherwise there were no differences in the disinfection protocols between sets for each method noted. MAIN OUTCOMES AND MEASURES: Effectiveness of various disinfection protocols in cleaning rigid nasal endoscopes experimentally inoculated with bacteria commonly found in the upper aerodigestive tract. Positive cultures following disinfection indicated ineffective or incomplete disinfection. RESULTS: Most cleaning methods were effective in eliminating S aureus, S pneumoniae, and H influenzae from the scopes following experimental contamination. Continued growth of P aeruginosa was found after all of the disinfection trials in experiment set A with the exception of a 10-minute immersion in Cidex OPA, and in set B except for the 10-minute Cidex OPA immersion and ABS plus IA trials. CONCLUSIONS AND RELEVANCE: Most cleaning methods used in our trials appear to properly disinfect RNEs after in vitro inoculation with S aureus, S pneumoniae, and H influenzae. However, it appears that disinfectants may be less effective in cleaning rigid scopes experimentally inoculated with P aeruginosa. There is a paucity of published data regarding cross-contamination during rigid nasal endoscopy, and these results should guide future studies and to some extent practice to avoid iatrogenic spread of contamination.

Potent nematicidal activity of phthalaldehyde, salicylaldehyde, and cinnamic aldehyde against Meloidogyne incognita.

The nematicidal activity of selected aromatic aldehydes was tested against the root knot nematode Meloidogyne incognita. The most active aldehyde was phthalaldehyde (1) with an EC(50) value of 11 ± 6 mg/L followed by salicylaldehyde (2) and cinnamic aldehyde (3) with EC(50) values of 11 ± 1 and 12 ± 5 mg/L, respectively. On the other hand, structurally related aldehydes such as 2-methoxybenzaldehyde (21), 3,4-dimethoxybenzaldehyde, and vanillin (23) were not active at the concentration of 1000 mg/L. By liquid chromatography-mass spectrometry the reactivity of tested aldehydes against a synthetic peptide resembling the nematode cuticle was characterized. At the test concentration of 1 mM, the main adduct formation was observed for 3,4-dihydroxybenzaldehyde (22), 2-methoxybenzaldehyde (21), and 3,4-dimethoxybenzaldehyde. Considering that 2-methoxybenzaldehyde (21) and 3,4-dimethoxybenzaldehyde were not active against M. incognita in in vitro experiments led us to hypothesize a different mechanism of action rather than an effect on the external cuticle modification of nematodes. When the toxicity of the V-ATPase inhibitor pyocyanin (10) was tested against M. incognita J2 nematodes, an EC(50) at 24 h of 72 ± 25 mg/L was found. The redox-active compounds such as phthalaldehyde (1) and salicylaldehyde (2) may share a common mode of action inhibiting nematode V-ATPase enzyme. The results of this investigation reveal that aromatic redox-active aldehydes can be considered as potent nematicides, and further investigation is needed to completely clarify their mode of action.

Bactericidal effects and cytotoxicity of new aromatic dialdehyde disinfectants (ortho-phthalaldehyde).

We investigated the bactericidal effects and cytotoxicity of an ortho-phthalaldehyde product in comparison with those of its predecessor glutaraldehyde products. Bactericidal effects ware examined on Mycobacterium terrae, a standard organism used for investigating the bactericidal effect of high-level disinfectants. Cytotoxicity as determined by the MTT assay was examined by using four cell lines. The colony forming test, a method to examine residual toxicity, and the evaporation test, a newly developed method to examine the toxicity of the evaporated ingredients, were performed. Test solutions were 2.25% and 3.5% glutaraldehyde (GA) products and a 0.55% ortho-phthalaldehyde (OPA) product, and glutaraldehyde itself. All the disinfectants showed sufficient bactericidal effects on M. terrae. Meanwhile, the OPA product was less toxic than GA products and GA itself to all the cell lines tested. The colony forming test showed that GA products and GA itself exerted residual cytotoxicity more potently than did the OPA product. The evaporation test showed that GA products and GA itself exerted cytotoxicity via evaporation more potently than did the OPA product. In conclusion, OPA appears to be less cytotoxic than GA even though bactericidal effects were comparable. This may be due to the lower concentration of the active ingredient (ortho-phthalaldehyde) in the OPA product.

Comparative biocidal activity of peracetic acid, benzalkonium chloride and ortho-phthalaldehyde on 77 bacterial strains.

Despite numerous reports on biocide activities, it is often difficult to have a reliable and relevant overview of bacterial resistance to disinfectants because each work challenges a limited number of strains and tested methods are often different. The aim of this study was to evaluate the bactericidal activity of three different disinfectants commonly used in industrial or medical environments (peracetic acid, benzalkonium chloride and ortho-phthalaldehyde) against 77 bacterial strains from different origins using one standard test method (NF EN 1040). Results highlight the existence of high interspecific variability of resistance to disinfectants and, contrary to widespread belief, Gram-positive strains generally appeared more resistant than Gram-negative strains. Resistance was also variable among strains of the same species such as Bacillus subtilis to peracetic acid, Pseudomonas aeruginosa to benzalkonium chloride and Staphylococcus aureus to ortho-phthalaldehyde.

Persister cells in a biofilm treated with a biocide.

This study investigated the physiology and behaviour following treatment with ortho-phthalaldehyde (OPA), of Pseudomonas fluorescens in both the planktonic and sessile states. Steady-state biofilms and planktonic cells were collected from a bioreactor and their extracellular polymeric substances (EPS) were extracted using a method that did not destroy the cells. Cell structure and physiology after EPS extraction were compared in terms of respiratory activity, morphology, cell protein and polysaccharide content, and expression of the outer membrane proteins (OMP). Significant differences were found between the physiological parameters analysed. Planktonic cells were more metabolically active, and contained greater amounts of proteins and polysaccharides than biofilm cells. Moreover, biofilm formation promoted the expression of distinct OMP. Additional experiments were performed with cells after EPS extraction in order to compare the susceptibility of planktonic and biofilm cells to OPA. Cells were completely inactivated after exposure to the biocide (minimum bactericidal concentration, MBC = 0.55 ± 0.20 mM for planktonic cells; MBC = 1.7 ± 0.30 mM for biofilm cells). After treatment, the potential of inactivated cells to recover from antimicrobial exposure was evaluated over time. Planktonic cells remained inactive over 48 h while cells from biofilms recovered 24 h after exposure to OPA, and the number of viable and culturable cells increased over time. The MBC of the recovered biofilm cells after a second exposure to OPA was 0.58 ± 0.40 mM, a concentration similar to the MBC of planktonic cells. This study demonstrates that persister cells may survive in biocide-treated biofilms, even in the absence of EPS.

Inactivation of surrogate coronaviruses on hard surfaces by health care germicides.

BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.

Role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium chelonae to aldehyde-based disinfectants and drugs.

Nosocomial outbreaks attributable to glutaraldehyde-resistant, rapidly growing mycobacteria are increasing. Here, evidence is provided that defects in porin expression dramatically increase the resistance of Mycobacterium smegmatis and Mycobacterium chelonae to glutaraldehyde and another aldehyde disinfectant, ortho-phthalaldehyde. Since defects in porin activity also dramatically increased the resistance of M. chelonae to drugs, there is thus some concern that the widespread use of glutaraldehyde and ortho-phthalaldehyde in clinical settings may select for drug-resistant bacteria.

Physicochemical and biological characterization of novel macrocycles derived from o-phthalaldehyde.

A series of novel macrocyclic compounds were synthesized by the condensation of o-phthalaldehyde with aromatic amino alcohols followed by treatment with 1,2-dibromoethane or 1,3-dibromopropane in non-template method. The structural features of the isolated macrocycles have been determined from the microanalytical, IR, (1)H, (13)C NMR and mass spectral studies. Antimicrobial activities of these macrocyclic compounds were tested against the gram-positive (Bacillus subtilis, Staphylococcus aureus) and gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria and found to exhibit potential antibacterial activity. The macrocycles were also tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus (A. flavus) and Fusarium species.

The role of oxidative stress in acrolein-induced DNA damage in HepG2 cells.

This study evaluated the role of oxidative stress in acrolein-induced DNA damage, using HepG2 cells. Using the standard single cell gel electrophoresis (SCGE) assay, a significant dose-dependent increment in DNA migration was detected at lower concentrations of acrolein; but at the higher tested concentrations, a reduction in the migration was observed. Post-incubation with proteinase K significantly increased DNA migration in cells exposed to higher concentrations of acrolein. These results indicated that acrolein caused DNA strand breaks and DNA-protein crosslinks (DPC). To elucidate the oxidatively generated DNA damage mechanism, the 2,7-dichlorofluorescein diacetate (DCFH-DA) and o-phthalaldehyde (OPT) were used to monitor the levels of reactive oxygen species (ROS) and glutathione (GSH), respectively. The present study showed that acrolein induced the increased levels of ROS and depletion of GSH in HepG2 cells. Moreover, acrolein significantly caused 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) formation in HepG2 cells. These results demonstrate that the DNA damage induced by acrolein in HepG2 cells is related to the oxidative stress.