Cargando…

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

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Catalano, Alessia, Iacopetta, Domenico, Rosato, Antonio, Salvagno, Lara, Ceramella, Jessica, Longo, Francesca, Sinicropi, Maria Stefania, Franchini, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922224/
https://www.ncbi.nlm.nih.gov/pubmed/33669633
http://dx.doi.org/10.3390/antibiotics10020204
_version_ 1783658641251893248
author Catalano, Alessia
Iacopetta, Domenico
Rosato, Antonio
Salvagno, Lara
Ceramella, Jessica
Longo, Francesca
Sinicropi, Maria Stefania
Franchini, Carlo
author_facet Catalano, Alessia
Iacopetta, Domenico
Rosato, Antonio
Salvagno, Lara
Ceramella, Jessica
Longo, Francesca
Sinicropi, Maria Stefania
Franchini, Carlo
author_sort Catalano, Alessia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7922224
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79222242021-03-03 Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban Catalano, Alessia Iacopetta, Domenico Rosato, Antonio Salvagno, Lara Ceramella, Jessica Longo, Francesca Sinicropi, Maria Stefania Franchini, Carlo Antibiotics (Basel) Article 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. MDPI 2021-02-19 /pmc/articles/PMC7922224/ /pubmed/33669633 http://dx.doi.org/10.3390/antibiotics10020204 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Catalano, Alessia
Iacopetta, Domenico
Rosato, Antonio
Salvagno, Lara
Ceramella, Jessica
Longo, Francesca
Sinicropi, Maria Stefania
Franchini, Carlo
Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title_full Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title_fullStr Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title_full_unstemmed Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title_short Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban
title_sort searching for small molecules as antibacterials: non-cytotoxic diarylureas analogues of triclocarban
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922224/
https://www.ncbi.nlm.nih.gov/pubmed/33669633
http://dx.doi.org/10.3390/antibiotics10020204
work_keys_str_mv AT catalanoalessia searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT iacopettadomenico searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT rosatoantonio searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT salvagnolara searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT ceramellajessica searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT longofrancesca searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT sinicropimariastefania searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban
AT franchinicarlo searchingforsmallmoleculesasantibacterialsnoncytotoxicdiarylureasanaloguesoftriclocarban