New pre-clinical evidence of anti-inflammatory effect and safety of a substituted fluorophenyl imidazole

Nascimento, Marcus Vinícius Pereira dos Santos; Munhoz, Antônio Carlos Mattar; Facchin, B.; Fratoni, Eduarda; Rossa, Thaís A.; Sá, Marcus M.; Campa, Carlo Cosimo; Ciraolo, Elisa; Hirsch, Emilio; Dalmarco, Eduardo Monguilhott

doi:10.1016/j.biopha.2019.01.052

Cited by 27 publications

(14 citation statements)

References 47 publications

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“…There is also a role for apoD in the regulation of inflammation and suggests that it protects from HVoV-OC43-induced encephalitis, probably through the phospholipase A2 signalling pathway (Do Carmo et al 2008 ). Some more recent developments are those directed to treat the acute respiratory distress syndrome (ARDS) (Dreher et al 2020 ), which shows inflammation due to acute hypoxemia and diffuse alveolar injury “following a triggering factor” (Santos Nasciemento et al 2019 ). These authors propose the development of fluorophenyl imidazole-derived molecules to treat pathologies, in which inflammation, in particular based on p38 MAPK and NFkB, plays a privotal role (Santos Nasciemento et al 2019 ).…”

Section: Implications For Neurodegenerative Disordersmentioning

confidence: 99%

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses

Riederer

Meulen

2020

J Neural Transm

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While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.

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Section: Implications For Neurodegenerative Disordersmentioning

confidence: 99%

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses

Riederer

Meulen

2020

J Neural Transm

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“…All the pretreatments were conducted orally (gavage), and after 1 h, all groups (except the Blank control) were anesthetized with xylazine/ketamine (5 mg/kg and 50 mg/kg) for intranasal LPS instillation (5 mg/kg in 50 μ L PBS). After 12 hours, mice were euthanized by an overdose of xylazine/ketamine and bronchoalveolar lavage fluid (BALF) was collected [13]. Immediately after the BALF collection, the total and differential leukocyte counts and exudate concentration (protein content) were performed.…”

Section: Methodsmentioning

confidence: 99%

Evidence That the Anti-Inflammatory Effect of Rubiadin-1-methyl Ether Has an Immunomodulatory Context

Mohr

Nascimento

Rosa

et al. 2019

Mediators of Inflammation

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Background In spite of the latest therapeutic developments, no effective treatments for handling critical conditions such as acute lung injuries have yet been found. Such conditions, which may result from lung infections, sepsis, multiple trauma, or shock, represent a significant challenge in intensive care medicine. Seeking ways to better deal with this challenge, the scientific community has recently devoted much attention to small molecules derived from natural products with anti-inflammatory and immunomodulatory effects. Aims In this context, we investigated the anti-inflammatory effect of Rubiadin-1-methyl ether isolated from Pentas schimperi, using an in vitro model of RAW 264.7 macrophages induced by LPS and an in vivo model of acute lung injury (ALI) induced by LPS. Methods The macrophages were pretreated with the compound and induced by LPS (1 μg/mL). After 24 h, using the supernatant, we evaluated the cytotoxicity, NOx, and IL-6, IL-1β, and TNF-α levels, as well as the effect of the compound on macrophage apoptosis. Next, the compound was administered in mice with acute lung injury (ALI) induced by LPS (5 mg/kg), and the pro- and anti-inflammatory parameters were analyzed after 12 h using the bronchoalveolar lavage fluid (BALF). Results Rubiadin-1-methyl ether was able to inhibit the pro-inflammatory parameters studied in the in vitro assays (NOx, IL-6, and IL-1β) and, at the same time, increased the macrophage apoptosis rate. In the in vivo experiments, this compound was capable of decreasing leukocyte infiltration; fluid leakage; NOx; IL-6, IL-12p70, IFN-γ, TNF-α, and MCP-1 levels; and MPO activity. In addition, Rubiadin-1-methyl ether increased the IL-10 levels in the bronchoalveolar lavage fluid (BALF). Conclusions These findings support the evidence that Rubiadin-1-methyl ether has important anti-inflammatory activity, with evidence of an immunomodulatory effect.

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“…Imidazole derivatives showed a wide scope of applicability in medicinal chemistry in recent years. Molecules bearing an imidazole moiety have become a promising antifungal [3], antibacterial [4,5], antituberculosis [6], and anti-inflammatory [7] agents. However, oncological diseases remain a major threat to the society due to their mutagenic and insidious nature [8,9].…”

Section: Introductionmentioning

confidence: 99%

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures

2021

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Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles. In this work, we have synthesized a series of new imidazole derivatives incorporating a benzenesulfonamide moiety in their structure, which then were evaluated for their cytotoxicity against human triple-negative breast cancer MDA-MB-231 and human malignant melanoma IGR39 cell lines by MTT assay. Benzenesulfonamide-bearing imidazole derivatives containing 4-chloro and 3,4-dichlorosubstituents in benzene ring, and 2-ethylthio and 3-ethyl groups in imidazole ring have been determined as the most active compounds. Half-maximal effective concentration (EC50) of the most cytotoxic compound was 27.8 ± 2.8 µM against IGR39 cell line and 20.5 ± 3.6 µM against MDA-MB-231 cell line. Compounds reduced cell colony formation of both cell lines and inhibited the growth and viability of IGR39 cell spheroids more efficiently compared to triple-negative breast cancer spheroids.

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New pre-clinical evidence of anti-inflammatory effect and safety of a substituted fluorophenyl imidazole

Cited by 27 publications

References 47 publications

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses

Evidence That the Anti-Inflammatory Effect of Rubiadin-1-methyl Ether Has an Immunomodulatory Context

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures

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