Novel Trifluoromethylcoumarinyl Urea Derivatives: Synthesis, Characterization, Fluorescence, and Bioactivity

Qiao, Lili; Hao, Shu

doi:10.3390/molecules23030600

Cited by 12 publications

(7 citation statements)

References 50 publications

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“…Thus, the desirable properties of next-generation antimicrobials should include broad-spectrum action and high efficacy toward pathogens but low toxicity to humans and should pose no risk of bioaccumulation. Recently, several diarylureas analogues of TCC were reported as antibacterial [ 18 ] and antifungal agents [ 19 ] bearing pentafluorosulfanyl and trifluoromethylcoumarine groups, respectively. As small molecules, their design should take into account a good oral bioavailability, following the “Lipinski’s rule of drug-likeness”, also named “the Rule of 5” (Ro5) [ 20 ].…”

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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“…Besides that, second absorption band which can observed at 343-352 nm was attributed as higher intensity compared (ε =62200 -82200 M -1 cm -1 ) to the first absorption band. It is due to the electronic transition produced from excitation of unsaturated moiety in a molecular structure [27]. Plus, excitation of π electrons from lower to higher energy levels by several unsaturated chromophores such as aromatic and carbonyl moieties was responsible for the transition [28].…”

Section: V(c-h) V(c=o) V(c=n)mentioning

confidence: 99%

Synthesis and Molecular Docking of 2,4,5-Trisubstituted-1,3-Thiazole Derivatives as Antibacterial Agents

2019

MJAS

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The emergence of antibiotic resistance against bacterial strains has attracted great interest in the discovery and development of new antibacterial agents. Thiazole derivatives have been widely used in the biological as well as pharmacological fields and their efficiency as pharmaceutical drugs are well established. In this study, a series of thiazole derivatives were synthesized in reaction between 3-chloroacetyl acetone and ammonium thiocyanate followed by incorporating selected amines in one-pot synthesis manner. The compounds were structurally characterized by Fourier Transform Infrared (FTIR), Proton Nuclear Magnetic Resonance ( 1 H NMR), Ultraviolet-Visible (UV-Vis) and Gas Chromatography-Mass Spectrometry (GC-MS). Their antibacterial properties were screened using disc diffusion technique against selected Gram-positive (Bacillus cereus and Staphylococcus epidermidis) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) with T3 exhibited the most potent antibacterial activity. Molecular docking studies were also performed against Glucosamine-6-phosphate (GlcN-6-P) synthase which is known as the essential building block of most bacteria. The docking result displayed that T3 exhibited the minimum binding energy of -7.09 kcal mol -1 as compared to T1 and T2 with -6.49 and -6.76 kcal mol -1 , respectively which is in agreement with antibacterial result. The output of this preliminary study will contribute in structural enhancement in drug discovery. AbstrakKewujudan rintangan terhadap bakteria telah menarik minat dalam penemuan dan perkembangan agen antibakteria yang terkini. Terbitan tiazol telah digunakan dengan meluas dalam bidang biologi dan farmakologi di mana keberkesanannya sebagai ubat farmaseutikal telah ditemui. Dalam kajian ini, terbitan tiazol telah disintesis dengan menindakbalaskan α-haloketon (3-kloroasetil aseton), ammonium tiosianat dan beberapa sebatian amina terpilih secara sintesis satu pot. Produk tindak balas yang terhasil telah dicirikan dengan Transformasi Fourier-Inframerah (FTIR), Proton Resonans Magnet Nukleus ( 1 H NMR), Ultralembayung-Sinar Nampak (UV-Vis) serta Kromatografi Gas-Spektrometer Jisim (GC-MS). Sifat antibakteria sebatian ini telah disaring menggunakan teknik serapan cakera terhadap bakteria Gram-positif (Bacillus cereus dan Staphylococcus epidermidis) dan Gram-negatif (Escherichia coli dan Pseudomonas aeruginosa) dengan T3 menunjukkan aktiviti antibakteria yang paling berkesan. Penyatuan molekul telah dilakukan terhadap enzim Glukosamina-6-fosfat sintase (GlcN-6-P) yang merupakan unsur binaan penting bagi kebanyakan bakteria. Merujuk kepada keputusan penyatuan molekul, T3 menunjukkan tenaga pengikatan yang paling minima iaitu -7.09 kcal mol -1 berbanding T1 dan T2 masing-masing pada -6.49 dan -6.76 kcal mol -1 , menunjukkan nilai-nilai ini bersetuju dengan keputusan saringan antibakteria. Keputusan kajian awal ini akan menyumbang kepada penambahbaikan struktur untuk penghasilan ubat.

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“…In this review, we will focus our attention on TCC, a small molecule also named 3,4,4′-trichlorocarbanilide that belongs to the class of diarylures or bis-arylureas. This interesting class of compounds has been recently reviewed by our research group as anticancer agents [ 6 ], and then, due to their multiple actions [ 7 , 8 , 9 , 10 , 11 ], they were also suggested for repositioning to antimicrobial agents and/or potential treatment for new pandemics, as COVID-19 [ 12 , 13 ]. TCC is a common ingredient in personal care products, especially dermal cleaning products such as antibacterial bar/Liquid soaps, body lotions, deodorants, detergents, medical disinfectants, aftershave soaps, hand sanitizers, toothpaste, handwash and mouthwash, body washes, cleansing lotions, baby teethers and wipes for its sanitizing properties and detergents [ 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this review, we will focus our attention on TCC, a small molecule also named 3,4,4trichlorocarbanilide that belongs to the class of diarylures or bis-arylureas. This interesting class of compounds has been recently reviewed by our research group as anticancer agents [6], and then, due to their multiple actions [7][8][9][10][11], they were also suggested for Since its advent in 1957 [22], TCC has been produced and used on a large scale, and its consumption from personal care products in the United States reached 500,000-1,000,000 pounds per year [23]. The 2013-2014 National Health and Nutrition Examination Survey showed that 36.9% of the urine samples in the United States (U.S.) contained TCC [24].…”

Section: Introductionmentioning

confidence: 99%

The Different Facets of Triclocarban: A Review

et al. 2021

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In the late 1930s and early 1940s, it was discovered that the substitution on aromatic rings of hydrogen atoms with chlorine yielded a novel chemistry of antimicrobials. However, within a few years, many of these compounds and formulations showed adverse effects, including human toxicity, ecotoxicity, and unwanted environmental persistence and bioaccumulation, quickly leading to regulatory bans and phase-outs. Among these, the triclocarban, a polychlorinated aromatic antimicrobial agent, was employed 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. Triclocarban has been widely used for over 50 years, but only recently some concerns were raised about its endocrine disruptive properties. In September 2016, the U.S. Food and Drug Administration banned its use in over-the-counter hand and body washes because of its toxicity. The withdrawal of triclocarban has prompted the efforts to search for new antimicrobial compounds and several analogues of triclocarban have also been studied. In this review, an examination of different facets of triclocarban and its analogues will be analyzed.

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Novel Trifluoromethylcoumarinyl Urea Derivatives: Synthesis, Characterization, Fluorescence, and Bioactivity

Cited by 12 publications

References 50 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

Synthesis and Molecular Docking of 2,4,5-Trisubstituted-1,3-Thiazole Derivatives as Antibacterial Agents

The Different Facets of Triclocarban: A Review

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