Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.

Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a key component of the cell wall, and its multistep biosynthetic process is an attractive antibacterial development target. Penicillin-binding proteins (PBPs) are responsible for cross-linking PG stem peptides, and their central role in bacterial cell wall synthesis has made them the target of successful antibiotics, including ß-lactams, that have been used worldwide for decades. Following the discovery of penicillin, several other compounds with antibiotic activity have been discovered and, since then, have saved millions of lives. However, since pathogens inevitably become resistant to antibiotics, the search for new active compounds is continuous. The present review highlights the ongoing development of inhibitors acting mainly in the transpeptidase domain of PBPs with potential therapeutic applications for the development of new antibiotic agents. Both the critical aspects of the strategy, design, and structure-activity relationships (SAR) are discussed, covering the main published articles over the last 10 years. Some of the molecules described display activities against main bacterial pathogens and could open avenues toward the development of new, efficient antibacterial drugs.

Optimized microwave-assisted extraction of polyphenols and tannins from Syzygium cumini (L.) Skeels leaves through an experimental design coupled to a desirability approach.

The present study consisted in optimizing the extractive method of polyphenols and total tannins of leaves of Syzygium cumini (L) Skeels assisted by microwaves to potentiate the antimicrobial activity of the dried extract of S. cumini against sensitive and resistant strains. A Box-Behnken design that consisted of 27 experimental runs coupled with a desirability function for multiple response optimization was employed to optimize the total polyphenols content and total tannins content. Antimicrobial sensitivity tests were evaluated by obtaining the minimum inhibitory concentration, minimum fungicidal concentration and minimum bactericidal concentration in 96-well petri dishes. The optimal extraction conditions were found to be 8 min of extraction, under 300 w of microwave power, using a 1:34 g/mL solid/solvent ratio and 38% of ethanol concentration as extraction solvent. The parameter with the greatest influence in the extraction was primarily the time, followed by the potency and proportion solid/solvent. This yielded a total polyphenol content of 87.37 ± 1.85 mg TAE g-1ext and a total tannin content of 79.68 ± 1.64 mg TAE g-1 ext. All tested microorganisms were sensitive to the extract, evidencing the effectiveness of the extraction method optimization.

Development of an analytical method for determination of polyphenols and total tannins from leaves of Syzygium cumini L. Skeels.

Syzygium cumini L. Skeels belongs to Myrtaceae family. This species has been recognized by its antidiabetic, anti-inflammatory, and antimicrobial activities. Despite ever-increasing scientific interest for this species there is no pharmacopeia method for characterization and standardization of S. cumini yet. So, toward this aim, the objective of this work was to develop an efficient analytical methodology able to determine polyphenols and tannins content from leaves hydroethanolic extract of S. cumini using Folin-Ciocalteu method by ultraviolet absorption spectrophotometry (UV-Vis). The analytical methodology was developed for the first time in the literature for leaves of this specie shown to be fast and low-cost with results expressed through tannic acid equivalent (TAE). Moreover, the methodology presented selectivity with maximum absorption at 706 nm wavelength, linearity with R2>0.99; limit of detection 0.275 µg TAE mL-1 and 0.102 µg TAE mL-1; limit of quantification 1.046 µg TAE mL-1 and 0.912 µg TAE mL-1 for total polyphenols and total tannins, respectively. Furthermore, the methodology was accurate with recover value greater than 98%, as well as exact, reproductive, and robust with coefficient of variation values less than 15% for both compounds. All the results are found within the fixed limits according to RDC 166/2017.

Antimicrobial Capacity of a Hydroxyapatite-Lysozyme-Lactoferrin-Lactoperoxidase Combination Against Streptococcus mutans for the Treatment of Dentinal Caries.

CONTEXT: Hydroxyapatite has shown to regenerate the mineralized layer of dentin, whereas the combination of the enzymes lysozyme, lactoferrin, and lactoperoxidase may exhibit antimicrobial properties against oral pathogens. AIMS: To evaluate a combination of hydroxyapatite and lysozyme, lactoferrin, and lactoperoxidase for the treatment of dentinal caries by measuring viable Streptococcus mutans. SETTINGS AND DESIGN: Laboratory study with experimental groups. METHODS AND MATERIAL: Carious lesions in 20 permanent third molars were treated with a combination of hydroxyapatite and the enzymes lysozyme, lactoferrin, and lactoperoxidase. Carious dentin was collected and homogenized in a vortex shaker. After homogenization, five decimal dilutions were performed. Three aliquots of 25 µL of each dilution were seeded onto the surface of mitis salivarius bacitracin (MSB) medium. All plates were incubated in anaerobic jars. After incubation, the viable bacterial count was determined. S. mutans counts were obtained before and 24 h, 1 month, and 6 months after treatment. STATISTICAL ANALYSIS USED: Descriptive statistical analysis and the Kruskal-Wallis test, supplemented by the Student-Newman-Keuls test. RESULTS: A significant reduction in S. mutans counts was observed 24 h after sealing with a combination of hydroxyapatite, lysozyme, lactoferrin, and lactoperoxidase as compared to counts after 1 month and after 6 months (P < 0.05). CONCLUSIONS: The combination of hydroxyapatite with lysozyme, lactoferrin, and lactoperoxidase may be an alternative for S. mutans control in dentinal caries.

Surtos de fotossensibilização e dermatite alérgica em ruminantes e equídeos no Nordeste do Brasil / Outbreaks of photosensitization and allergic dermatitis in ruminants and equidae in northeastern Brazil

O presente estudo foi conduzido com o objetivo de determinar as causas de fotossensibilização em ruminantes e equídeos no Nordeste do Brasil, através da revisão dos laudos de exames arquivados no Laboratório de Patologia Veterinária da Universidade Federal da Paraíba. Durante os quatro anos do estudo foram diagnosticados 22 surtos de fotossensibilização, incluindo 11 surtos de fotossensibilização primária e oito surtos de fotossensibilização hepatógena. A intoxicação por Froelichia humboldtiana foi a principal causa de fotossensibilização e a única causa de fotossensibilização primária. As espécies mais gravemente afetadas por fotossensibilização primária foram os asininos, caprinos, bovinos e ovinos, mas os equinos e mulas também são afetados. A intoxicação por Brachiaria decumbens foi a principal causa de fotossensibilização hepatógena e afetou apenas os ovinos e bovinos. Outras plantas associadas com fotossensibilização hepatógena incluíram Enterolobium contortisiliquum e Lantana camara. Dermatite alérgica foi diagnosticada em dois rebanhos ovinos e em um cavalo. Os animais tinham lesões crônicas, caracterizadas por alopecia, crostas e hiperpigmentação no topo da cabeça, ao redor dos olhos (ovinos) e nos membros (equino). O prurido foi o principal sinal clínico observado nos casos de fotossensibilização primária e hipersensibilidade à picada de insetos.(AU)

The study was conducted to determine the causes of photosensitization in ruminants and equidae in northeastern Brazil through a review of the files at the Laboratório de Patologia Veterinária of Universidade Federal da Paraíba. During four years of the study 22 outbreaks of photosensitization were diagnosed, including 11 outbreaks of primary photosensitization and eight outbreaks of hepatogenous photosensitization. Poisoning by Froelichia humboldtiana was the main cause of photosensitization, and the only cause of primary photosensitization. The most severely affected animals by primary photosensitization are donkeys, goats, cattle and sheep, but horses and mules may also be affected. Poisoning by Brachiaria decumbens was the main cause of hepatogenous photosensitization, and affected only sheep and cattle. Other plants associated with hepatogenous photosensitization in cattle include Enterolobium contortisiliquum and Lantana camara. Allergic dermatitis was diagnosed in two flocks of sheep and in a horse. The animals had chronic lesions characterized by areas of alopecia, crusts and hyperpigmentation on the head, around the eyes (sheep) and at the legs (horse). Itching was the main clinical sign in cases of primary photosensitization and insect hypersensitivity.(AU)

Primary photosensitization caused by ingestion of Froelichia humboldtiana by dairy goats.

This study aimed to describe the first report of an outbreak of primary photosensitization in dairy goats caused by Froelichia humboldtiana. The disease occurred from March to May 2014, in a mixed flock of 15 Saanen, Alpine, and crossbred lactating goats. The entire flock was affected; however, the Saanen and cross-bred goats developed more severe lesions, and their milk production decreased by as much as 75%. Lesions were progressive and consisted of skin hyperemia, edema, and necrosis, especially in depigmented areas. An experimental study with two goats resulted in photodermatitis, similar to that observed in the natural cases, 10-14 days after the beginning of plant ingestion. Serum activities of aspartate aminotransferase (AST) and -glutamyltransferase (GGT) and, direct, indirect, and total bilirubin serum concentrations were within the normal ranges. In conclusion, F. humboldtiana causes primary photosensitization in goats with a negative impact on milk production.

Structure and Growth of Hexagonal Boron Nitride on Ir(111).

Using the X-ray standing wave method, scanning tunneling microscopy, low energy electron diffraction, and density functional theory, we precisely determine the lateral and vertical structure of hexagonal boron nitride on Ir(111). The moiré superstructure leads to a periodic arrangement of strongly chemisorbed valleys in an otherwise rather flat, weakly physisorbed plane. The best commensurate approximation of the moiré unit cell is (12 × 12) boron nitride cells resting on (11 × 11) substrate cells, which is at variance with several earlier studies. We uncover the existence of two fundamentally different mechanisms of layer formation for hexagonal boron nitride, namely, nucleation and growth as opposed to network formation without nucleation. The different pathways are linked to different distributions of rotational domains, and the latter enables selection of a single orientation only.