Facile synthesis of triphenylenes and triphenylene/phenanthrene fused heteroaromatics.

In the recent past, development of milder, safer and comparatively less toxic methods in organic synthesis has received great attention. We report a simple and facile method for the synthesis of substituted triphenylenes and their heteroaryl analogues using ceric ammonium nitrate (CAN) via oxidative biaryl coupling. We describe the structural and photophysical properties of these unique heteroaryl fused triphenylenes.

Peptide Functionalized Metallic Nanoconstructs: Synthesis, Structural Characterization, and Antimicrobial Evaluation.

Biomolecule based conjugation of metallic nanoparticles has become an important area of research lately especially considering the role of such nanoconjugates in diverse applications. Herein, synthesis of cationic dipeptide conjugated gold/silver nanoparticles through the covalent approach using carbodiimide cross-linker chemistry has been reported. Owing to the exceptional optoelectronic properties of metallic nanoparticles, peptide-gold/silver nanoparticle conjugates were synthesized employing 2-mercaptopropanoic acid as a cross-linker. The conjugates were further compared with their noncovalently synthesized counterparts using ultraviolet-visible spectroscopy. It was generally observed that the conjugates synthesized using the covalent approach were more stable than the conventional noncovalent approach. The synthesized conjugates were further evaluated for their antimicrobial efficacy. The experimental findings demonstrated that peptide capped silver nanoparticles possessed relatively better antimicrobial activity than peptide capped gold nanoparticles, native peptides as well as unconjugated gold/silver nanoparticles which was also evident in time kill assay studies. The morphological effects of active compounds on Escherichia coli and Candida albicans exhibited complete disruption of the cell wall. Thus, this study is an important step toward the opening up of avenues for the applicability of the covalent approach for functionalization of metallic nanoparticles with not only short peptide based systems but also for other biomolecules in areas such as anti-infectives, drug delivery, and bioimaging.

Bioactive nano-metal-organic frameworks as antimicrobials against Gram-positive and Gram-negative bacteria.

More effective antibiotics are needed to overcome the problem of multidrug resistance. The antibacterial efficacies of three Zn-based nano metal-organic frameworks (nMOFs) - IRMOF-3, MOF-5, and Zn-BTC - were explored, both alone and as mixtures with ampicillin and kanamycin. When tested against Escherichia coli, Staphylococcus aureus, Staphylococcus lentus, and Listeria monocytogenes, the nMOF/drug mixtures demonstrated synergistic (IRMOF-3/kanamycin) or additive (other nMOF/drug combinations) effects compared with the nMOFs or antibiotics alone. Zn-Based nMOFs can reduce the burden of the new discovery of antimicrobial pharmaceuticals by increasing the potency of existing antibiotics.

Stabilized cationic dipeptide capped gold/silver nanohybrids: Towards enhanced antibacterial and antifungal efficacy.

The nanoparticles of silver/gold and cationic peptides have been recognized as potent antimicrobials for long, but their combined effect has so far not been explored. The present study reports the green synthesis of short cationic dipeptide stabilized AuNPs/AgNPs based nanohybrid materials. It thoroughly investigates the effect of conjugation of short cationic peptides on the antimicrobial properties of metallic nanoparticles. In the context of the antimicrobial evaluation of synthesized nanoconjugates, it was observed that peptide capped AgNPs exhibited higher antimicrobial activity as compared to peptide capped AuNPs as well as native peptides and unconjugated metallic nanoparticles. Specifically, l-His-l-Arg-OMe capped AgNPs exhibited MIC of 0.50, 0.37 and 0.25µM against E.coli, S. aureus and S. typhimurium respectively and MIC of 0.80 and 10.00µM against C. albicans and C. glabrata respectively. These results indicate that synthetic dipeptides render AgNPs as better antimicrobial agents in comparison to the native AgNPs and positively charged dipeptides. In addition, the time kill profile of cationic peptide (l-His-l-Arg-OMe) capped AgNPs was found to be even better than the known antibiotics. The cytotoxic behavior of all synthesized nanoconjugates of cationic peptides was studied and was found to be within acceptable limits. The present study opens a completely new class of antimicrobials for combating a wide range of bacterial and fungal pathogens. Another interesting and crucial finding was that dipeptide capped AgNPs displayed maximum antimicrobial activity with observed approximate 2-10 fold reduction in nano formulation dosage against tested microbes.

Improved oral therapeutic potential of nanoencapsulated cryptdin formulation against Salmonella infection.

An encapsulated system for cryptdin-2 (a Paneth cell antimicrobial peptide) was developed, with a view to help it sustain adverse gut conditions and to ensure its bioavailability on oral administration. The formulation was characterized on the basis of particle size, zeta potential and polydispersity index. Cryptdin-2 loaded nanoparticles of size 105±7 nm, formulated by ionotropic gelation method using chitosan: tripolyphosphate (5:2), revealed 60% drug entrapment efficiency with 65% in vitro release in 4.5 h. Developed system was evaluated for its therapeutic application against Salmonella Typhimurium infection in mice, on the basis of survivability of animals, bacterial load in tissues, histo-architecture and oxidative damage markers. Infected mice when treated with the encapsulated peptide showed 83% survivability and approximately 2 log unit reductions in the bacterial load in the tissues versus 100% mortality observed with the free peptide. The encapsulated cryptdin-2 also achieved a decrease in the level of oxidants, particularly nitrite by 3.25 folds and increased the level of antioxidant catalase by 2 folds when compared to the levels exhibited by the free peptide. The bacteriological and biochemical alterations illustrated by encapsulated peptide co-related well with the histo-architectural studies. The study is a first pre-clinical report on the oral effectiveness of cryptdin-2 by its suitable encapsulation and has potential for future clinical applications.

Immuno-fluorescence based Vi capsular polysaccharide detection for specific recognition of Salmonella enterica serovar Typhi in clinical samples.

Typhoid fever is a life threatening bacterial infection that remains a major global health concern. This continued high burden associated with significant morbidity and mortality rate demands specific and rapid detection technique. This work reports a new sandwich type fluorescence immunoassay format using polymyxin B, a cationic receptor molecule, as a binder agent while anti-Vi antibody served as the capturing agent for specifically detecting Salmonella enterica serovar Typhi. Anti-Vi IgG antibody raised against Vi-BSA conjugate revealed affinity of 7.779nM(-1) signifying immunodominancy of O-acetyls groups in Vi polysaccharide. The detection limit of the developed assay was around 10(1) cellsmL(-1) of Vi expressing Salmonella enterica serovar Typhi with a correlation coefficient (R(2)) equal to 0.97. Positive response obtained for all the tested serovar Typhi clinical isolates as well as the pathogen spiked blood samples recommended specificity and accuracy of Vi antigen as a biomarker during typhoid fever. The intra- and inter-assay precision with Vi spiked samples were satisfactory revealing coefficient of variance (CV%) with a mean of 4.05% and 5.97% respectively. This may be the novel attempt and constructive report on the fluorescence based detection of Vi antigen of serovar Typhi in the epidemic as well as pandemic outbreaks.

Structure-activity relationships of monoterpenes and acetyl derivatives against Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUND: Dengue fever virus transmitted by Aedes aegypti causes lethal mortalities of human beings, and, because of the lack of any vaccine, management of this vector, especially with phytochemicals, is essential. In the present investigation, the structure-activity relationship of monoterpenes and their acetyl derivatives was studied to identify structural features that are responsible for mosquitocidal activity. RESULTS: Derivatization of monoterpenes (eugenol, geraniol, linalool, L-menthol and terpeniole) followed by structure-activity relationship studies identified all five acetyl derivatives as having enhanced mosquitocidal activity against fourth-instar larvae of Aedes aegypti. Acetylation of the hydroxyl group in general increased activity in comparison with hydroxyl compounds. Based on LC50 values (ppm), the activities could be placed in the following order: eugenyl acetate (50.2) > linalyl acetate (119.7) > terpinyl acetate (287.1) > menthyl acetate (308.4) > geranyl acetate (325.5), as compared with monoterpenoids: eugenol (82.8) > linalool (242.6) > terpineol (331.7) > L-menthol (365.8) > geraniol (415.0). In eugenyl acetate, the presence of an aromatic ring and a side chain with an allylic double bond makes it most effective. CONCLUSION: Bioactive functional groups identified in the study may contribute to the understanding of larvicidal activity of acetyl derivatives and may help in the development of ecofriendly mosquito larvicidal compounds.

Immunological characterization of recombinant Salmonella enterica serovar Typhi FliC protein expressed in Escherichia coli.

Like any other enteric pathogen, Salmonella also encounters acidic stress in the stomach as well as within the host macrophage milieu. However, the pathogen is reported to combat this stress through acid tolerance response (ATR), expressing a number of genes and eventually the proteins. Recently, an acid induced outer membrane phenotype encoded by fliC gene in Salmonella enterica serovar Typhi has been identified. In the present study, fliC gene was cloned to study its biological implications. The recombinant FliC (rFliC) protein was observed to stimulate the production of antibodies. These antibodies could also recognize the FliC protein (antigen) in the clinical samples i.e. blood samples from typhoid patents as well as healthy blood samples spiked with serovar Typhi. Moreover, the rFliC also reacted with the sera from patients suffering with typhoid fever indicating its in-vivo immunogenicity. Ex-vivo study revealed that rFliC has the potential to stimulate the macrophages to generate higher levels of inflammatory mediators such as malondialdehyde (MDA) and nitrite. The inflammatory potential of FliC was also confirmed in-vivo, by the paw oedema test as well as by flicking response of the inflamed paw indicating hyperalgesia occurring during inflammatory response. The findings of the present study indicate that acid induced FliC might be one of the factors enhancing the virulence of serovar Typhi under the host acidic conditions and may prove to be helpful in designing the prophylactic measures.