A set of small nonpeptidic diaryl phosphonate inhibitors was prepared. Some of these inhibitors show potent and highly selective irreversible uPA inhibition. The biochemical and modeling data prove that the combination of a benzylguanidine moiety with a diaryl phosphonate ester results in optimized molecules for derivatizing the serine alcohol in the uPA active site. Selected compounds show significant antimetastatic effects in the BN-472 rat mammary carcinoma model. We report in this paper a preclinical proof of concept that selective, irreversible uPA inhibitors could be valuable in antimetastatic therapy.

Sliding wear evaluation of nanostructured coatings deposited by Suspension High Velocity OxyFuel (S-HVOF) and conventional HVOF (Jet Kote (HVOF-JK) and JP5000 (HVOF-JP)) spraying were evaluated. S-HVOF coatings were nanostructured and deposited via an aqueous based suspension of the WC-Co powder, using modified HVOF (TopGun) spraying. Microstructural evaluations of these hardmetal coatings included X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray Spectroscopy (EDX). Sliding wear tests on coatings were conducted using a ball-on-flat test rig against steel, silicon nitride (Si 3 N 4 ) ceramic and WC-6Co balls. Results indicated that nanosized particles inherited from the starting powder in S-HVOF spraying were retained in the resulting coatings. Significant changes in the chemical and phase composition were observed in the S-HVOF coatings. Despite decarburization, the hardness and sliding wear resistance of the S-HVOF coatings was comparable to the HVOF-JK and HVOF-JP coatings. The sliding wear performance was dependent on the ball-coating test couple. In general a higher ball wear rate was observed with lower coating wear rate. Comparison of the total (ball and coating) wear rate indicated that for steel and ceramic balls, HVOF-JP coatings performed the best followed by the S-HVOF and HVOF-JK coatings. For the WC-Co ball tests, average performance of S-HVOF was better than that of HVOF-JK and HVOF-JP coatings. Changes in sliding wear 1 Corresponding author R.Ahmed@hw.ac.uk 2 behavior were attributed to the support of metal matrix due to relatively higher tungsten, and uniform distribution of nanoparticles in the S-HVOF coating microstructure. The presence of tribofilm was also observed for all test couples.

The release of harmful wastes via different industrial activities is the main cause of heavy metal toxicity. The present study was conducted to assess the effects of heavy metal stress on the plant growth traits, antioxidant enzyme activities, chlorophyll content and proline content of Sesbania sesban with/without the inoculation of heavy-metal-tolerant Bacillus gibsonii and B. xiamenensis. Both PGP strains showed prominent ACC-deaminase, indole acetic acid, exopolysaccharides production and tolerance at different heavy metal concentrations (50–1000 mg/L). Further, in a pot experiment, S. sesban seeds were grown in contaminated and noncontaminated soils. After harvesting, plants were used for the further analysis of growth parameters. The experiment comprised of six different treatments. The effects of heavy metal stress and bacterial inoculation on the plant root length; shoot length; fresh and dry weight; photosynthetic pigments; proline content; antioxidant activity; and absorption of metals were observed at the end of the experiment. The results revealed that industrially contaminated soils distinctly reduced the growth of plants. However, both PGPR strains enhanced the root length up to 105% and 80%. The shoot length was increased by 133% and 75%, and the fresh weight was increased by 121% and 129%. The proline content and antioxidant enzymes posed dual effects on the plants growing in industrially contaminated soil, allowing them to cope with the metal stress, which enhanced the plant growth. The proline content was increased up to 190% and 179% by the inoculation of bacterial strains. Antioxidant enzymes, such as SOD, increased to about 216% and 245%, while POD increased up to 48% and 49%, respectively. The results clearly show that the utilized PGPR strains might be strong candidates to assist S. sesban growth under heavy metal stress conditions. We highly suggest these PGPR strains for further implementation in field experiments.

This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC(50) of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.

Mucormycosis is considered one of the most dangerous invasive fungal diseases. In this study, a facile, green and eco-friendly method was used to biosynthesize silver nanoparticles (AgNPs) using Pseudomonas indica S. Azhar, to combat fungi causing mucormycosis. The biosynthesis of AgNPs was validated by a progressive shift in the color of P. indica filtrate from colorless to brown, as well as the identification of a distinctive absorption peak at 420 nm using UV-vis spectroscopy. Fourier-transform infrared spectroscopy (FTIR) results indicated the existence of bioactive chemicals that are responsible for AgNP production. AgNPs with particle sizes ranging from 2.4 to 53.5 nm were discovered using transmission electron microscopy (TEM). Pattern peaks corresponding to the 111, 200, 220, 311, and 222 planes, which corresponded to face-centered cubic forms of metallic silver, were also discovered using X-ray diffraction (XRD). Moreover, antifungal activity measurements of biosynthesized AgNPs against Rhizopus Microsporus, Mucor racemosus, and Syncephalastrum racemosum were carried out. Results of antifungal activity analysis revealed that the biosynthesized AgNPs exhibited outstanding antifungal activity against all tested fungi at a concentration of 400 µg/mL, where minimum inhibitory concentrations (MIC) were 50, 50, and 100 µg/mL toward R. microsporus, S. racemosum, and M. racemosus respectively. In addition, the biosynthesized AgNPs revealed antioxidant activity, where IC50 was 31 µg/mL when compared to ascorbic acid (0.79 µg/mL). Furthermore, the biosynthesized AgNPs showed no cytotoxicity on the Vero normal cell line. In conclusion, the biosynthesized AgNPs in this study can be used as effective antifungals with safe use, particularly for fungi causing mucormycosis.

The potential to improve the tribomechanical performance of HVOF-sprayed WC-12Co coatings was studied by using aqueous WC-12Co suspensions as feedstock. Both as-sprayed and hot-isostatic-pressed (HIPed) coatings were studied. Mathematical models of wear rate based on the structure property relationships, even for the conventionally sprayed WC-Co hardmetal coatings, are at best based on the semiempirical approach. This paper aims to develop these semiempirical mathematical models for suspension sprayed nanocomposite coatings in as-sprayed and heat-treated (HIPed) conditions. Microstructural evaluations included transmission electron microscopy, X-ray diffraction and scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy. The nanohardness and modulus of the coated specimens were investigated using a diamond Berkovich nanoindenter. Sliding wear tests were conducted using a ball-on-flat test rig. Results indicated that the HIPing post-treatment resulted in crystallization of amorphous coating phases and increase in elastic modulus and hardness. Influence of these changes in the wear mechanisms and wear rate is discussed. Results are also compared with conventionally sprayed high-velocity oxy-fuel hardmetal WC-Co coatings.

The global spread of multidrug-resistant bacteria has become a significant hazard to public health, and more effective antibacterial agents are required. Therefore, this study describes the preparation, characterization, and evaluation of gold nanoparticles modified with chitosan (Chi/AuNPs) as a reducing and stabilizing agent with efficient antimicrobial effects. In recent years, the development of an efficient and ecofriendly method for synthesizing metal nanoparticles has attracted a lot of interest in the field of nanotechnology. Colloidal gold nanoparticles (AuNPs) were prepared by the chemical reduction of gold ions in the presence of chitosan (Chi), giving Chi/AuNPs. The characterization of Chi/AuNPs was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and X-ray diffraction (XRD). Chi/AuNPs appeared spherical and monodispersed, with a diameter ranging between 20 to 120 nm. The synergistic effects of AuNPs and Chi led to the disruption of bacterial membranes. The maximum inhibitory impact was seen against P. aeruginosa at 500 µg/mL, with a zone of inhibition diameter of 26 ± 1.8 mm, whereas the least inhibitory effect was reported for S. aureus, with a zone of inhibition diameter of 16 ± 2.1 mm at the highest dose tested. Moreover, Chi/AuNPs exhibited antifungal activity toward Candida albicans when the MIC was 62.5 µg/mL. Cell viability and proliferation of the developed nanocomposite were evaluated using a sulphorhodamine B (SRB) assay with a half inhibitory concentration (IC50) of 111.1 µg/mL. Moreover, the in vitro wound-healing model revealed that the Chi/AuNP dressing provides a relatively rapid and efficacious wound-healing ability, making the obtained nanocomposite a promising candidate for the development of improved bandage materials.

A number of new 5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazole derivatives, 2 -5 and 8 -11, were synthesized. The 2-{5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazol-2-ylthio}acetohydrazones 6a and 6b were synthesized by the reaction of the hydrazide 4 with the corresponding monosaccharides. Cyclization of the sugar hydrazones 6a and 6b with acetic anhydride afforded the substituted oxadiazoline derivatives 7a and 7b. The synthesized compounds were evaluated for their antiviral activity against, the human immunodefi ciency virus (HIV-1) and some of these compounds showed moderate to high antiviral activity.