Synthesis and preliminary biological evaluation of antibacterial and antifungal 5-arylidene tetramic acid-cadmium(II) complexes.

The synthesis and biological evaluation of 5-arylidene-N-acetyl-tetramic acids cadmium(II) complexes are reported. Eleven novel compounds were prepared, characterized by nuclear magnetic resonance experiments and screened for their antimicrobial activity against five bacterial species (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus [MRSA]) and two fungi (Candida albicans and Cryptococcus neoformans). The complexes showed similar or enhanced activities against MRSA in comparison to the corresponding ligands and, additionally, promising antifungal activities against C. neoformans. The most active compounds 3c and 3h showed remarkable activities against MRSA (minimum inhibitory activity [MIC] values of 32 and 4 µg/ml, respectively) and C. neoformans (MIC values of 8 and 16 µg/ml, respectively), accompanied by no human cell toxicity and hemolytic activity within the tested concentration range. The results demonstrate that appropriately functionalized tetramic acids attached with lipophilic alkanoyl chain and after complexation with cadmium(II) ions may act as valuable lead compounds for further investigations toward the development of novel antibacterial and/or antifungal agents.

Isolated Gallbladder Injury Secondary to Blunt Abdominal Trauma.

A 60-year-old male was admitted to our major level 1 trauma centre following a fall from the fourth storey of a car park and landing initially on his feet on concrete. The primary survey was unremarkable apart from abdominal pain and localised peritonism in the right upper quadrant and lower lumbar midline pain. The secondary survey revealed bilateral complex calcaneal fractures, multiple vertebral fractures and sternal fracture. A trauma CT scan showed pericholecystic fluid and described by the radiology team either as cholecystitis picture or possible disruption of the gallbladder wall. Based on the patient's stable presentation, the decision was made for a diagnostic laparoscopy to explore possible gallbladder injury and other concomitant injuries.  Operative findings showed free bile in the right upper quadrant and right paracolic gutter and small amount of blood. The gallbladder did not have an obvious site of perforation but had a necrotic appearance. No further injuries identified laparoscopically after checking small and large bowel, and since no obvious perforation was identified, the decision was made to convert to laparotomy and duodenal exploration. On laparotomy, there was no evidence of duodenal or pancreatic injury on Kocher's manoeuvre and ligament of Trietz mobilisation. The gall bladder wall was stained and leaking bile, therefore a standard retrograde cholecystectomy was performed. No further intra-abdominal injuries were identified during the laparotomy. The patient made an unremarkable recovery. He was discharged home with physiotherapy for rehabilitation. We recommend a diagnostic laparoscopy and cholecystectomy for such injuries with a low threshold for duodenal exploration (Kocherization) if the perforation site is not obvious based on the high incidence of concomitant duodenal injuries.

Synthesis, biological evaluation and structure-activity relationships of 5-arylidene tetramic acids with antibacterial activity against methicillin-resistant Staphylococcus aureus.

The steady rise of the antimicrobial resistance is a major global threat to human health that requires the urgent need for novel antibiotics. In this work we report the synthesis of a small library of 3-subsituted-5-arylidene tetramic acids in order to investigate the scope of our previously established methodology via an intermediate oxazolone and their antimicrobial activity. From this series of 14 tetramic acids, 11 derivatives are novel and one of them is a Schiff base, which was structurally characterized with single-crystal X-ray analysis and NMR spectroscopy. The compounds incorporating a lipophilic acyl group at carbon-3 of the ring showed moderate to high activity with minimum inhibitory activity of 4-32 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), accompanied by no human cell toxicity and hemolytic activity within the tested concentration range. The substituent at para position of the aryl ring seemed to have no or little effect on the antimicrobial activity of these compounds.

Synthesis, characterization and antimicrobial activity of N-acetyl-3-acetyl-5-benzylidene tetramic acid-metal complexes. X-ray analysis and identification of the Cd(II) complex as a potent antifungal agent.

This study aims at the further expansion of knowledge on the antimicrobial activities of the tetramic acid moiety and the effect of metal complexation. Complexes of the N-acetyl-3-acetyl-5-benzylidenetetramic acid with Mn, Co, Ni, Cu, Zn and Cd were synthesized and screened against 5 key ESKAPE pathogens (Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) and 2 fungi (Cryptococcus neoformans and Candida albicans). The cadmium complex was found to effectively inhibit the fungus Cryptococcus neoformans with minimum inhibitory concentration (MIC) of 8 µg/mL, with no human cell toxicity and hemolytic activity within the tested concentration range. The biologically active tetramic acid­cadmium complex was structurally characterized by single-crystal X-ray analysis. Furthermore, the thermal stability of the ligand and the complexes was investigated along with NMR and EPR studies of the Cd(II) and Co(II) complexes respectively.

X-Ray Crystallographic Analysis, EPR Studies, and Computational Calculations of a Cu(II) Tetramic Acid Complex.

In this work we present a structural and spectroscopic analysis of a copper(II) N-acetyl-5-arylidene tetramic acid by using both experimental and computational techniques. The crystal structure of the Cu(II) complex was determined by single crystal X-ray diffraction and shows that the copper ion lies on a centre of symmetry, with each ligand ion coordinated to two copper ions, forming a 2D sheet. Moreover, the EPR spectroscopic properties of the Cu(II) tetramic acid complex were also explored and discussed. Finally, a computational approach was performed in order to obtain a detailed and precise insight of product structures and properties. It is hoped that this study can enrich the field of functional supramolecular systems, giving place to the formation of coordination-driven self-assembly architectures.

Demonstration of Calreticulin Expression in Hamster Pancreatic Adenocarcinoma with the Use of Fluorescent Gold Quantum Dots.

BACKGROUND: There is dire need for discovery of novel pancreatic cancer biomarkers and of agents with the potential for simultaneous diagnostic and therapeutic capacity. This study demonstrates calreticulin expression on hamster pancreatic adenocarcinoma via bio-conjugated gold quantum dots (AuQDs). MATERIALS AND METHODS: Hamster pancreatic adenocarcinoma cells were cultured, fixed and incubated with fluorescent AuQDs, bio-conjugated to anti-calreticulin antibodies. Anti-calreticulin and AuQDs were produced in-house. AuQDs were manufactured to emit in the near-infrared. Cells were further characterized under confocal fluorescence. RESULTS: AuQDs were confirmed to emit in the near-infrared. AuQD bio-conjugation to calreticulin was confirmed via dot-blotting. Upon laser excitation and post-incubation with bio-conjugated AuQDs, pancreatic cancer cell lines emitted fluorescence in near-infrared. CONCLUSION: Hamster pancreatic cancer cells express calreticulin, which may be labelled with AuQDs. This study demonstrates the application of nanoparticle-based theranostics in pancreatic cancer. Such biomarker-targeting nanosystems are anticipated to play a significant role in the management of pancreatic cancer.