COVID-19: Could Irisin Become the Handyman Myokine of the 21st Century?

Catalano, Alessia

doi:10.2174/2666796701999200617154655

Cited by 25 publications

(17 citation statements)

References 104 publications

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“…Triclocarban, N-(4-chlorophenyl)-N'- (3,4-dichlorophenyl)urea, is a highly effective and broad spectrum antimicrobial that has been successfully used in personal care products for over 60 years [3]. It belongs to the privileged class of diarylureas, which have been recently extensively reviewed for their multiple actions, including the anticancer [4], and have also been proposed for a repositioning as antimicrobial agents and/or for the treatment of new pandemics, including COVID-19 [5,6]. It is predominantly found in household necessities and personal care products, especially dermal cleaning products such as antibacterial bar/liquid soap, body lotion, deodorants, aftershave soaps, hand sanitizers, toothpaste, handwash and mouthwash [7].…”

Section: Introductionmentioning

confidence: 99%

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

et al. 2021

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Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as soaps, toothpaste and shampoo. In September 2016, the U.S. FDA banned nineteen antimicrobial ingredients, including TCC, in over-the-counter consumer antiseptic wash products, due to their toxicity. Withdrawal of TCC has prompted efforts to search for new antimicrobial compounds. In this paper, we present the synthesis and biological evaluation, as antibiotic and non-cytotoxic agents, of a series of diarylureas, analogues of TCC. These compounds are characterized by an intriguingly simple chemistry and can be easily synthesized. Among the synthesized compounds, 1ab and 1bc emerge as the most interesting compounds as they show the same activity of TCC (MIC = 16 µg/mL) against Staphylococcus aureus, and a higher activity than TCC against Enterococcus faecalis (MIC = 32 µg/mL versus MIC = 64 µg/mL). Moreover, 1ab and 1bc show no cytotoxicity towards the human mammary epithelial cells MCF-10A and embryonic kidney epithelial cells Hek-293, in opposition to TCC, which exhibits a marked cytotoxicity on the same cell lines and shows a good antitumor activity on a panel of cell lines tested.

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Section: Introductionmentioning

confidence: 99%

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

et al. 2021

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“…Thus, a drug delivery system for sorafenib has been recently studied in order to help the administration of therapies in malignant cells and raise its clinical efficacy [40]. Recently, the treatment of cancers of the gastrointestinal tract during the COVID-19 pandemic [41] has been studied: coronavirus-adapted institutional recommendations have been formulated. Sorafenib was recommended in the first-line setting only in patients with disease subtype Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 and Child-Pughscore A hepatocellular carcinoma [42].…”

Section: Sorafenibmentioning

confidence: 99%

Diarylureas as Antitumor Agents

et al. 2021

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The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties. Some diarylureas, serine-threonine kinase or tyrosine kinase inhibitors, were recently reported in literature. The first to come into the market as an anticancer agent was sorafenib, followed by some others. In this review, we survey progress over the past 10 years in the development of new diarylureas as anticancer agents.

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“…It is known that the novel coronavirus pneumonia is closely associated with inflammatory storms. Indeed, the patients with severe COVID-19 have a “cytokine storm” syndrome, given the high-levels of pro-inflammatory cytokines found in these patients [ 26 ]. Moreover, there is an increasing recognition of a prothrombotic state in COVID-19 [ 27 ] and neuropsychiatric diseases such as depression and anxiety [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

et al. 2021

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Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.

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COVID-19: Could Irisin Become the Handyman Myokine of the 21st Century?

Cited by 25 publications

References 104 publications

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

Diarylureas as Antitumor Agents

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

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