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

Abstract

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.

Environmental impact of increased soap consumption during COVID-19 pandemic: Biodegradable soap production and sustainable packaging

“…Incorporating such chemical elements into hand hygiene products can substantially increase the extent of human exposure to them and can cause unexpected health risks. Moreover, the intentional or unintentional disposal release of these chemical elements contaminates the environment ( Catalano et al, 2021 ). As a cross-sectional study, Alhazmi et al reported that 34.8% of the participants used antibacterial soap against the coronavirus ( Alhazmi et al, 2019 ).…”

The Different Facets of Triclocarban: A Review

“…The compounds 3 and 4 described by Sarveswari et al (2018) [ 112 ] showed the same activity of the standard (ciprofloxacin) against the Gram-negative Proteus mirabilis (ATCC 19181) (zone of inhibition of 23 and 24 mm, respectively, at a concentration of 200 µg/mL compared to 30 mm of ciprofloxacin). Catalano et al (2021) [ 71 ] described the properties of a series of diarylureas analogues of TCC: six compounds ( 5 – 10 ) showed the same activity of TCC against S. aureus (MIC = 16 µg/mL). Out of the six, particularly interesting were the compounds 5 and 6 that also demonstrated even higher activity than TCC against E. faecalis (MIC = 32 µg/mL versus MIC = 64 µg/mL of TCC).…”

“…Recently, Pujol et al (2018) [70] determined the MIC value for TCC against Staphylococcus aureus ATCC 12600 (MIC = 0.5 µg/mL) and found that it was the same as ciprofloxacin. In a successive paper, the MIC value for TCC was 16 µg/mL against S. aureus ATCC 29213 and 6538P (versus 0.5-2 µg/mL of norfloxacin) [71]. Although TCC has been widely used as an antimicrobial for over 50 years, it was only recently that concerns were raised about its endocrine disruptive properties.…”

Special Issue on “Anticancer Drugs Activity and Underlying Mechanisms”

“…Again, Catalano et al [24] reviewed the different properties of diarylureas [8,25], namely ureas bearing two aromatic moieties as substituents, focusing on their role as important pharmacophore in anticancer drugs over the past 10 years. A clinically used member of this class, sorafenib was the lead compound approved from Food and Drug Administration (FDA) and the European Medicinal Agency (EMEA) for the treatment of advanced metastatic hepatocellular carcinoma and advanced renal cell carcinoma, paving the way to other diarylureas derivatives, such as regorafenib, linifanib, tivozanib and ripretinib, which share the ability to inhibit the kinases.…”