Mariappan Premanathan

Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation

UNLABELLED Nanoparticles are increasingly recognized for their utility in biological applications including nanomedicine. The present study investigated the toxicity of zinc oxide (ZnO) nanoparticles toward prokaryotic and eukaryotic cells. Cytotoxicity of ZnO to mammalian cells was studied using human myeloblastic leukemia cells (HL60) and normal peripheral blood mononuclear cells (PBMCs). Antibacterial activity of ZnO was also tested against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, as well as the Gram-positive bacterium Staphylococcus aureus, and the effect was more pronounced with the Gram-positive than the Gram-negative bacteria. ZnO nanoparticles exhibited a preferential ability to kill cancerous HL60 cells as compared with normal PBMCs. The nanoparticles enhanced ultrasound-induced lipid peroxidation in the liposomal membrane. The work suggested two mechanisms underlying the toxicity of ZnO: (i) involvement of the generation of reactive oxygen species (ROS) and (ii) induction of apoptosis. The work also revealed potential utility of ZnO nanoparticles in the treatment of cancer, for their selective toxicity to cancer cells. FROM THE CLINICAL EDITOR The toxicity of zinc oxide to bacteria was related to the generation of reactive oxygen species and to the induction of apoptosis. Interestingly, these effects were differentially greater in human myeloblastic leukemia cells (HL60) than normal peripheral blood mononuclear cells.

Antiviral properties of a mangrove plant, Rhizophora apiculata Blume, against human immunodeficiency virus.

A polysaccharide extracted from the leaf of Rhizophora apiculata (RAP) was assessed in cell culture systems, for its activity against human and simian immunodeficiency viruses. RAP inhibited HIV-1 or HIV-2 or SIV strains in various cell cultures and assay systems. It blocked the expression of HIV-1 antigen in MT-4 cells and abolished the production of HIV-1 p24 antigen in peripheral blood mononuclear cells (PBMC); the 50% effective concentration (EC50) of RAP in HIV-1 infected MT-4 cells and in PBMC was 10.7 and 25.9 microg/ml, respectively. RAP (100 microg/ml) completely blocked the binding of HIV-1 virions to MT-4 cells. RAP also reduced the production of viral mRNA when added before virus adsorption. RAP inhibited syncytium formation in cocultures of MOLT-4 cells and MOLT-4/HIV-1(IIIB) cells. RAP did not prolong activated partial thromboplastin time (APTT) up to 500 microg/ml. These properties may be advantageous should RAP be considered for further development.

Synthesis of polymethacrylate derivatives having sulfated maltoheptaose side chains with anti‐HIV activities

Anti-HIV (human immunodeficiency virus) active polymethacrylates having pendant sulfated oligosaccharides were synthesized, and the relationship between structures and biological activities of the polymethacrylates was examined. Acetylated 1-O-methacryloyl maltoheptaoside (MA-AcM7) was polymerized with AIBN as an initiator to give polymethacrylates having a pendant acetylated maltoheptaose in every repeating unit, poly(MA-AcM7)s. After hydroxyl groups were recovered by deacetylation, the polymethacrylates having maltoheptaose units, poly(MA-M7)s, were sulfated to give polymethacrylates having sulfated maltoheptaose side-chains, poly(MA-SM7)s, with degrees of sulfation of 1.1 to 2.7 (maximum, 3.0). These polymethacrylates including sulfated oligosaccharides exhibited low anti-HIV activities represented by the 50% protecting concentration (EC 50 ) in the range of 15-62 μg/mL and low blood anticoagulant activities around 10 unit/mg (standard dextran sulfate, 22.7 unit/mg). The anti-HIV activity increased with increasing degree of sulfation to reach EC 50 of 15-16 μg/mL. In addition, copolymerization of MA-AcM7 with methyl methacrylate (MMA) and subsequent sulfation gave polymethacrylates consisting of various proportions of highly sulfated maltoheptaose and MMA units. It was revealed that the anti-HIV activity increased with decreasing proportion of the sulfated oligosaccharide moiety and that a copolymethacrylate having 22 mol % of sulfated maltoheptaose units (DS = 3.0) had a high anti-HIV activity in the EC 50 of 0.3 μg/mL. The blood anticoagulant activity increased slightly from 9 to 18 unit/mg with decreasing proportion of the sulfated maltoheptaose units. These results suggested that the biological activities were influenced strongly by the spatial distance between sulfated oligosaccharide substituents in the polymethacrylate main chain. Distinction and conformation of the oligosaccharide side chains also played an important role.

Nanostructured molybdenum oxide-based antibacterial paint: effective growth inhibition of various pathogenic bacteria

The prevention of bacterial infections in the health care environment is paramount to providing better treatment. Covering a susceptible environment with an antimicrobial coating is a successful way to avoid bacterial growth. Research on the preparation of durable antimicrobial coatings is promising for both fundamental surface care and clinical care applications. Herein, we report a facile, efficient, and scalable preparation of MoO3 paint using a cost-effective ball-milling approach. The MoO3 nanoplates (synthesized by thermal decomposition of ammonium heptamolybdate) are used as a pigment and antibacterial activity moiety in alkyd resin binders and other suitable eco-friendly additives in the preparation of paint. Surface morphology, chemical states, bonding nature, and intermolecular interaction between the MoO3 and the alkyd resin were studied using Raman and x-ray photoelectron spectroscopic analysis. The antibacterial properties of a prepared MoO3 nanoplate against various bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae) was determined using the microdilution method. Bacterial strains exposed to an MoO3 paint coated surface exhibit a significant loss of viability in a time-dependent manner. Fundamental modes of antibacterial activities ascribed from a biocompatible and durable MoO3 nanostructure incorporated into an alkyd resin complex are discussed. The obtained experimental findings suggest the potential utility of prepared MoO3-based paint coating for the prevention of health care associated infections.

SYNTHESIS OF SULFONATED AMINO-POLYSACCHARIDES HAVING ANTI-HIV AND BLOOD ANTICOAGULANT ACTIVITIES

Sulfonated 3-amino-3-deoxy-(1-->6)-alpha-D-allopyranans were synthesized to elucidate the relationship between structure and such specific biological activities as anti-HIV and blood anticoagulant activities. Ring-opening copolymerization of 1,6-anhydro-3-azido-2,4-di-O-benzyl-3-deoxy-beta-D-allopyranose 1 with 1,6-anhydro- 2,3,4-tri-O-benzyl-beta-D-allopyranose 2 with PF5 catalyst gave copolymers having various proportions of the 1 unit. 13C NMR spectroscopy showed the resulting copolymers to have alpha-(1-->6)-stereoregularity, and the monomer reactivity ratios were calculated to be r1 = 0.92 and r2 = 1.11 by the Kelen-Tüdös method. Reduction of the azido groups and subsequent debenzylation of the copolymers afforded new amino-polysaccharides consisting of 3-amino-3-deoxy-allose and allose units. Sulfonation of 3-amino-3-deoxy-(1-->6)-alpha-D-allopyranan and copolysaccharides consisting of 3-amino-allose and allose or glucose units was performed with piperidine-N-sulfonic acid to give polysaccharides containing sulfoamido and sulfonate groups in good yields. The sulfoamido-copolysaccharides containing of 3-amino-3-deoxy-allose and glucose units exhibited high anti-HIV activities manifested by the 50% protecting concentration (EC50) of 0.2-0.5 mg/mL and low cytotoxicity shown by a 50% cytotoxic concentration (CC50) of > 1000 micrograms/mL. The sulfoamido-copolysaccharides containing 3-amino-allose and allose units had somewhat lower anti-HIV activities (EC50 = 0.8-0.9 microgram/mL) and slightly higher cytotoxicities (CC50 = 740-797 micrograms/mL). In addition, it was found that the blood anti-coagulant activity increased, with increasing proportion of the amino-allose unit, from 30 to 58 unit/mg (standard dextran sulfate, 22.7 unit/mg). These results suggest that the sulfonated 3-amino-3-deoxyallose unit plays important roles on both anti-HIV and blood anticoagulant activities.

Synthesis and biological activity of N-acylphenothiazines

Previous studies have demonstrated the relationship between radical intensity and cytotoxic activity in water-soluble compounds. This relationship was investigated in lipophilic compounds. Several N-acylphenothiazines showed higher cytotoxic activity against human leukemic and squamous carcinoma cell lines than phenothiazine, the parent compound. Electron spin resonance (ESR) spectroscopy showed that these active compounds produced much lower amounts of radicals than phenothiazine. Several compounds failed to inhibit the cytopathic effects of human immunodeficiency virus (HIV) infection in MT-4 cells. It suggested that the radical-mediated-mechanisms has not involved in the induction of cytotoxic activity by lipophilic compounds, such as N-acylphenothiazines.

Synthesis, anticancer and antioxidant activities of 7-methoxyisoflavanone and 2,3-diarylchromanones

A convenient, fast and high yielding method for the preparation of 7-methoxyisoflavanone and 2,3-diarylchromanones has been developed by the condensation of benzyl-2-hydroxy-4-alkoxyphenylketone with arylaldehyde/paraformaldehyde in presence of diethylamine, assisted by microwave activation. All the synthesized compounds were screened for anticancer as well as antioxidant activities. Among the nine compounds, 7-methoxyisoflavanone 7 and diarylchromanone 6c shows potential anticancer activity and diarylchromanone 6b has potential antioxidant activity. Compound 6h possesses anticancer and antioxidant activity at the same concentration.

INDUCTION OF APOPTOSIS AND ANTI-HIV ACTIVITY BY TANNIN- AND LIGNIN-RELATED SUBSTANCES

Tannins and lignins are two major classes of polyphenolic compounds widely distributed in the plant kingdom. Tannins are largely classified into hydrolyzable and condensed tannins.1 Hydrolyzable tannins have structures in which a polyalcohol (mainly glucose) is esterified with polyphenolic carboxylic acids, such as galloyl, hexahydroxydiphenoyl (HHDP) (a dimer of the galloyl group), valoneoyl (a trimer of the galloyl group), or dehydrohexahydroxydiphenoyl groups (an oxidized metabolite of the HHDP group). Condensed tannins are composed of flavan units, mostly (+)-catechin, (−)-epieatechin, or their analogues, condensed with each other via carbon-carbon bonds.

3-(5-Dimethylamino-1-Naphthalenesulphonyl)-2-(3-Pyridyl)Thiazolidine (YHI-1) Selectively Inhibits Human Immunodeficiency virus Type 1:

3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidine (YHI-1), a synthetic analogue of D-cysteinolic acid isolated from sardines (Sardinops melanostictus), was found to be a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in various cell cultures. YHI-1 inhibited HIV-1IIIB replication with a 50% effective concentration (EC50) of 3.35, 10.23 and 4.61 μM in MT-4 cells, peripheral blood mononuclear cells and MAGI-CCR5 cells, respectively. However, no antiviral activity was observed with non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 strains, such as nevirapine-resistant HIV-1HE/NEV and MKC-442-resistant HIV-1IIIB-R, or with HIV-2ROD or SIVMAC. YHI-1 failed to inhibit reverse transcriptase (RT) activity in vitro with different template–primer systems. Time-of-addition experiments, the failure to inhibit NNRTI-resistant strains and the failure to show in vitro activity against RT suggest that a metabolite of YHI-1 inside the cell acts like an NNRTI. Thus, YHI-1 seems to belong to a new class of HIV-1 inhibitor and is a good candidate for further development.

Distribution of biocide resistant genes and biocides susceptibility in multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii — A first report from the Kingdom of Saudi Arabia

PURPOSES The aim of this study was to determine the frequency of biocide resistant genes, qacA, qacE and cepA in multidrug resistant (MDR) bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii and to correlate the presence or absence of resistant genes with biocides susceptibility. MATERIALS AND METHODS The study included 44 MDR K. pneumoniae, P. aeruginosa and A. baumannii microorganisms. The bacteria were screened for the presence of biocide resistant genes by the polymerase chain reaction (PCR) method. The test organisms were isolated from various clinical specimens in the Qassim region, Saudi Arabia. The in vitro susceptibility tests of the three biocides (benzalkonium chloride, cetrimide and chlorhexidine gluconate) were studied against the test isolates by broth microdilution method following Clinical and Laboratory Standards Institute guidelines. RESULTS With the distribution of biocide resistant genes in K. pneumoniae, all 9 isolates (100%) possessed cepA; 4 (44.4%) and 1 (11.1%) isolate contained qacA and qacE genes respectively. Among 24 isolates of A. baumannii tested, cepA, qacA and qacE genes were found in 54.2%, 16.7% and 33.3% of isolates respectively. Among 11 P. aeruginosa isolates, 63.6% contained cepA gene, 18.2% contained qacE genes, and none of the isolates harboured qacA gene. There was no significant correlation between presence or absence of biocide resistant genes and high MIC values of the test isolates (p≥0.2). CONCLUSION Our observations imply that there was no significant correlation between presence or absence of biocide resistant genes and MICs observed in MDR K. pneumoniae, P. aeruginosa and A. baumannii. Further studies are required to find to confirm the trend of reduced susceptibility to biocides of problematic nosocomial pathogens.