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A simple, accurate and fast method was developed for the assessment of 3-nitrotyrosine as a biomarker for the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) using a (Eu(TTA)3Phen) photo probe. 3-Nitrotyrosine can remarkably quench the luminescence intensity of the (Eu(TTA)3Phen) complex in DMSO at pH = 9 and λ em = 617 nm. The quenching of the luminescence intensity of (Eu(TTA)3Phen) complex particularly the electrical emission band at λ em = 617 nm is used for the assessment of 3-nitrotyrosine in different serum samples of patients with liver cirrhosis.
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The alarming reduction in drug effectiveness against bacterial infections has created an urgent need for the development of new antibacterial agents that circumvent bacterial resistance mechanisms. We report here a series of DNA gyrase and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of 0.06 µg mL-1 against fluoroquinolone-resistant Staphylococcus aureus. Although in vitro hERG and CYP inhibition precluded further development, it validates a rational design approach to address this urgent unmet medical need and provides a scaffold for further optimisation, which is presented in part 2.
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Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC90 of 0.5 µg mL-1 against Staphylococcus aureus, favourable in vitro pharmacokinetic properties, selectivity versus human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.
RESUMO
AIM: This study aimed to determine the prevalence rates of Mycobacterium infection in camel sera collected before slaughter and gross lesion tissue collected postmortem (PM) using enzyme-linked immunosorbent assay (ELISA), bacteriological culture, and polymerase chain reaction (PCR). In addition, serum samples from humans who had occupational contact with camels were tested by ELISA and sputum sample by culture. MATERIALS AND METHODS: ELISA was performed on serum samples antemortem. In addition, bacteriological culture and PCR were conducted after PM. Tuberculosis infection was identified in humans who had contact with camels using ELISA for serum samples and culture for sputum samples. RESULTS: Tuberculous lesions were detected in 184 of 10,903 camels (1.7%). The ELISA results revealed that of the 184 examined camel serum samples, 124 (67.39%) were positive and all 20 camel serum samples that had no associated tuberculous lesions were negative. Moreover, only one of 48 (2.08%) human serum samples was positive by ELISA. Mycobacterial culture revealed 112 isolates from the 184 examined camel samples (60.87%), while human sputum sample cultures were all negative. PCR analysis identified the mpb70 gene in three of seven randomly tested samples. CONCLUSION: Gene sequencing was performed on two samples and the sequences were submitted to the National Center for Biotechnology Information GenBank (accession numbers MF990289 and MG59479). A phylogenetic tree was constructed based on the partial DNA sequences of the mpb70 gene; the similarity between the isolates was 98.1%. The similarities between the two isolates and the standard strains of Mycobacterium bovis in GenBank were 98.1% and 100%, respectively. Further investigation on the antemortem detection of M. bovis infection in camels is needed to decrease public risk.
