Role of myeloid cells in ischemic retinopathies: recent advances and unanswered questions.

Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal pathologies and recent studies suggest that targeting myeloid cells is a promising therapeutic strategy to mitigate diabetic retinopathy and other ischemic retinal diseases. This review summarizes the recent advances in our understanding of the role of microglia and macrophages in retinal diseases and focuses on the effects of myeloid cells on neurovascular injury and angiogenesis in ischemic retinopathies. We highlight gaps in knowledge and advocate for a more detailed understanding of the role of myeloid cells in retinal ischemic injury to fully unlock the potential of targeting myeloid cells as a therapeutic strategy for retinal ischemia.

Fluoroquinolones' Biological Activities against Laboratory Microbes and Cancer Cell Lines.

Development of novel derivatives to rein in and fight bacteria have never been more demanding, as microbial resistance strains are alarmingly increasing. A multitude of new fluoroquinolones derivatives with an improved spectrum of activity and/or enhanced pharmacokinetics parameters have been widely explored. Reporting novel antimicrobial agents entails comparing their potential activity to their parent drugs; hence, parent fluoroquinolones have been used in research as positive controls. Given that these fluoroquinolones possess variable activities according to their generation, it is necessary to include parent compounds and market available antibiotics of the same class when investigating antimicrobial activity. Herein, we provide a detailed guide on the in vitro biological activity of fluoroquinolones based on experimental results published in the last years. This work permits researchers to compare and analyze potential fluoroquinolones as positive control agents and to evaluate changes occurring in their activities. More importantly, the selection of fluoroquinolones as positive controls by medicinal chemists when investigating novel FQs analogs must be correlated to the laboratory pathogen inquest for reliable results.

Fluoroquinolones structural and medicinal developments (2013-2018): Where are we now?

Fluoroquinolones are considered one of the widely utilized antibiotics, specifically, with the recent development of newer generations such as moxifloxacin, delafloxacin and finafloxacin which possess a wider spectrum of activity and improved bioavailability. However, alarming increase in bacterial resistance reports worldwide incites medicinal chemists to employ guided-biologically-oriented-synthesis-strategies toward the modulation of quinolones derivatives activity. At present, quinolone scaffold diverse biological activities prompted the fortuitous discovery of novel antimicrobial and anticancer derivatives. Herein, the opponent arguments (2013-2015) regarding the structure activity relationships of fluoroquinolones' antibacterial, anticancer, antifungal activities are inscribed.

Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents.

In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid-D-(+)-glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL-1458 was carried out. In vitro antimicrobial assay revealed that 1-ethyl-7-methyl-4-oxo-N-(1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide (5) and 1-ethyl-7-methyl-4-oxo-N-(2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.

RNA Coronaviruses' Outbreaks: Recent Progress on the SARS-CoV-2 Pandemic Diagnostic Tests, Vaccination and Therapeutics.

Coronaviruses are RNA-infective viruses that could be considered principal players in universal high-profile outbreaks, namely the Severe Acute Respiratory Syndrome (SARS, 2002-2003), the Middle East Respiratory Syndrome (MERS, 2012) and the continuing novel coronavirus disease (COVID-19, 2019) pandemic. RNA coronaviruses infections raise public health concerns with infections' severity ranging from serious pandemics and highly contagious infections to common influenza episodes. With a wide consensus concerning the seminal role of early detection of the infectious agent on the clinical prognosis, recent technological endeavors have facilitated the rapid, sensitive and specific diagnosis of viral infections. Given that the burst of confirmed cases of the novel coronavirus disease 2019 (COVID-19) are climbing steeply, and we are amid this pandemic, this work will center at the respiratory RNA-viruses outbreaks, including the three coronaviruses-related pandemics, emphasizing on the approved diagnostic approaches, outlining therapeutic clinical trials as well as vaccine candidates. Based on the accumulated data and knowledge on the previous RNA-virus outbreaks, this review aspires to link the current intervention measures against SARS-CoV-2 infection with the previous interventions and to provide a roadmap for any possible future measures.

Design, synthesis and antimicrobial evaluation of novel glycosylated-fluoroquinolones derivatives.

Herein we report the design, synthesis and biological evaluation of structurally modified ciprofloxacin, norfloxacin and moxifloxacin standard drugs, featuring amide functional groups at C-3 of the fluoroquinolone scaffold. In vitro antimicrobial testing against various Gram-positive bacteria, Gram-negative bacteria and fungi revealed potential antibacterial and antifungal activity. Hybrid compounds 9 (MIC 0.2668 ± 0.0001 mM), 10 (MIC 0.1358 ± 00025 mM) and 13 (MIC 0.0898 ± 0.0014 mM) had potential antimicrobial activity against a fluoroquinolone-resistant Escherichia coli clinical isolate, compared to ciprofloxacin (MIC 0.5098 ± 0.0024 mM) and norfloxacin (MIC 0.2937 ± 0.0021 mM) standard drugs. Interestingly, compound 10 also exerted potential antifungal activity against Candida albicans (MIC 0.0056 ± 0.0014 mM) and Penicillium chrysogenum (MIC 0.0453 ± 0.0156 mM). Novel derivatives and standard fluoroquinolone drugs exhibited near-identical cytotoxicity levels against L6 muscle cell-line, when measured using the MTT assay.