Echiumin E, an Aryl Dihydronaphthalene Lignan from the Australian Invasive Plant Paterson's Curse (Echium plantagineum).

A new aryl dihydronaphthalene lignan, echiumin E (1), and four known compounds, echiumin A, globoidnan A, (-)-rabdosiin, and rosmarinic acid (2-5), were isolated from the Australian invasive plant Echium plantagineum (Paterson's curse) for the first time. Echiumin E (1) was characterized by 1D/2D NMR spectroscopy and MS spectrometry, with its absolute configuration assigned through comparison of experimental and TDDFT-calculated ECD data. Echiumin E (1) along with compounds 3-5 were screened in vitro against three cancer cell lines (SH-SY5Y, HeLa, and PC-3) and a prostate stromal (normal) cell line (WPMY-1) using a resazurin reduction assay. Echiumin E (1) was found to be active toward HeLa cells (IC50 0.21 µM).

Design, synthesis and bioactivity evaluation of novel pyrazole linked phenylthiazole derivatives in context of antibacterial activity.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a significant burden both clinically and economically worldwide. Increasing resistance to current antibiotics requires an urgent investigation into novel classes of antimicrobial agents. This study presents a structure-activity relationship (SAR) rationale for pyrazole linked phenylthiazole analogues as new antibacterial agents. A library of 23 novel pyrazole linked phenylthiazole compounds were synthesised, followed by screening for antimicrobial activity against five bacterial species and two fungi. The most active compound 14b has shown promising antibacterial activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) strain (MIC 4 µg/mL). Furthermore, the active pyrazole linked phenylthiazole compound exhibited a better toxicity profile than standard antibiotics. In summary, these results demonstrate that a pyrazole linked phenylthiazole scaffold has potential as a lead for further investigation to afford novel antibacterial agents.

A new approach towards the synthesis of pseudaminic acid analogues.

The pseudaminic acids are a family of 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids that are essential components of bacterial polysaccharides and glycoproteins. This paper describes our approach towards the synthesis of analogues of pseudaminic acid, and involves the efficient introduction of the requisite nitrogen functionalities from a readily available precursor.

Intravenous antimicrobial administration through peripheral venous catheters - establishing risk profiles from an analysis of 5252 devices.

INTRODUCTION: Peripheral venous catheters (PVCs) are used to administer antimicrobials, but many fail prior to completion of therapy. While some antimicrobials are known to increase the PVC failure rate, risk profiles for many are unclear. OBJECTIVE: To synthesize data from prospective PVC studies conducted between 2013 and 2019 to determine associations between common antimicrobials and PVC failure. METHODS: A secondary analysis was undertaken of seven randomized controlled trials and two prospective cohort studies from three quaternary hospitals (two adult and one paediatric) in Australia between 2013 and 2019. The primary outcome was PVC failure due to vessel injury (occlusion, infiltration or extravasation) or irritation (pain or phlebitis). Associations between antimicrobial use and PVC failure were explored using multi-variable Cox regression. RESULTS: In total, 5252 PVCs (4478 patients) were analysed; vessel injury and irritations occurred in 19% and 11% of all PVCs, respectively. Vessel injury was significantly associated with cefepime hydrochloride [hazard ratio (HR) 2.50; 95% confidence interval (CI) 1.44-4.34], ceftazidime pentahydrate (HR 1.91, 95% CI 1.11-3.31), flucloxacillin sodium (HR 1.84, 95% CI 1.45-2.33), lincomycin hydrochloride (HR 1.67, 95% CI 1.10-2.52) and vancomycin hydrochloride (HR 1.73, 95% CI 1.25-2.40). Irritation was significantly associated with flucloxacillin sodium (HR 2.58, 95% CI 1.96-3.40). CONCLUSIONS: This study identified several antimicrobials associated with increased PVC failure, including some that were already known to be associated and some that had not been identified previously. Research is needed urgently to determine superior modes of delivery (e.g. dilution, infusion time, device type) that may prevent PVC failure.

Antioxidant Properties and Reported Ethnomedicinal Use of the Genus Echium (Boraginaceae).

The genus Echium L. from the Boraginaceae family consists of 67 recognised species. The genus is widely distributed in the Mediterranean, having been documented in the traditional medicine of the area since 300 B.C. Current pharmacological studies have validated early ethnomedicinal properties showing that Echium spp. possesses antioxidant, analgesic, anxiolytic, anti-inflammatory, antibacterial, and antiviral effects. Nevertheless, only limited papers report specifically on the phytochemistry of this genus. Furthermore, the potential of utilising extracts from Echium species as natural antioxidant preparations has been significantly neglected. For the first time, this review comprehensively describes and discusses the presence of recorded Echium species with ethnomedicinal uses, their antioxidative properties in vitro and in vivo when available, and major phytochemical components recognised as potent antioxidants, as well as the possibilities and opportunities for future research.

Simplified Novel Muraymycin Analogues; using a Serine Template Strategy for Linking Key Pharmacophores.

The present status of antibiotic research requires the urgent invention of novel agents that act on multidrug-resistant bacteria. The World Health Organization has classified antibiotic-resistant bacteria into critical, high and medium priority according to the urgency of need for new antibiotics. Naturally occurring uridine-derived "nucleoside antibiotics" have shown promising activity against numerous priority resistant organisms by inhibiting the transmembrane protein MraY (translocase I), which is yet to be explored in a clinical context. The catalytic activity of MraY is an essential process for bacterial cell viability and growth including that of priority organisms. Muraymycins are one subclass of naturally occurring MraY inhibitors. Despite having potent antibiotic properties, the structural complexity of muraymycins advocates for simplified analogues as potential lead structures. Herein, we report a systematic structure-activity relationship (SAR) study of serine template-linked, simplified muraymycin-type analogues. This preliminary SAR lead study of serine template analogues successfully revealed that the complex structure of naturally occurring muraymycins could be easily simplified to afford bioactive scaffolds against resistant priority organisms. This study will pave the way for the development of novel antibacterial lead compounds based on a simplified serine template.

Caprazamycins: Promising lead structures acting on a novel antibacterial target MraY.

The present status of antibiotic resistant requires an urgent invention of novel agents that act on clinically unexplored antibacterial targets. The enzyme MraY (phospho-MurNAc-pentapeptide translocase), essential for bacterial cell wall synthesis, fulfils this criterion as it has not been explored as a target in a clinical context. Specifically, the enzyme is involved in the lipid-linked cycle of peptidoglycan biosynthesis and is reportedly targeted by naturally-occurring nucleoside antibiotics. The antimicrobial 'caprazamycin' class of nucleoside antibiotics targets Mycobacterium tuberculosis and clinically relevant Gram-negative bacteria such as Pseudomonas aeruginosa besides various drug resistant strains and is therefore an eligible starting point for the development of novel agents. In this review, we aim to summarise the structure-activity relationships of the natural, semi-synthetic as well as synthetic analogues of nucleoside antibiotic caprazamycins. This review highlights caprazamycins as promising lead structures for development of potent and selective antimicrobial agents that target MraY, the bacterial enzyme involved in the first membrane-dependent step in bacterial peptidoglycan assembly.

Protection against Radiotherapy-Induced Toxicity.

Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.