1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies

Gündüz, Miyase Gözde; Uğur, Sümeyye Buran; Güney, Funda Özdemir; Özkul, Ceren; Krishna, Vagolu Siva; Kaya, Serpil; Sriram, Dharmarajan; Doğan, Şengül Dilem

doi:10.1016/j.bioorg.2020.104104

Cited by 25 publications

(15 citation statements)

References 22 publications

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“…In addition, adsorption, distribution, metabolism and excretion (ADME) properties and physiochemical properties of the synthesized analogs were calculated using molinspiration cheminformatics [ 45 , 46 ]. Additionally, percentage absorption and drug-likeness model score were also calculated using the reported formula [ 47 ] and Molsoft [ 48 ], respectively. As indicated by the TPSA values (between 60 and 160Å 2 ), all the analogs ( 6aa – df ) possessed better intestinal absorption ability over the blood–brain barrier (BBB) penetration power.…”

Section: Resultsmentioning

confidence: 99%

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

et al. 2021

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A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as 1H and 13C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC50 values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC50 values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC50 = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC50 = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

et al. 2021

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“…This study showed the targeted activity indirectly, by considering only the virulence genes downstream of the ComA protein and that the comA gene was not downregulated. On the other hand, recent studies have shown that different derivatives from 1,3-disubstituted urea possess anti-biofilm activity against Pseudomonas aeruginosa , Mycobacterium tuberculosis and Candida albicans [ 47 ]. These derivatives appear to specifically bind to the LasR protein, as reported by in silico docking studies [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, recent studies have shown that different derivatives from 1,3-disubstituted urea possess anti-biofilm activity against Pseudomonas aeruginosa , Mycobacterium tuberculosis and Candida albicans [ 47 ]. These derivatives appear to specifically bind to the LasR protein, as reported by in silico docking studies [ 47 ]. Therefore, it is clear that 1,3-disubstituted urea derivatives can impart their biological activity against different species and kingdoms through a wide range of single or multitargeted interactions, which remain to be dissected in detail.…”

Section: Resultsmentioning

confidence: 99%

A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

et al. 2020

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An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.

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“…[17] In another report, urea 10 was found to have high antibacterial activity. [7] Moreover, Gunduz et al revealed that another urea derivative 11, has very high antibacterial activity against the bacterial strain of Pseudomonas aeruginosa [18] (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Gunduz et al. revealed that another urea derivative 11 , has very high antibacterial activity against the bacterial strain of Pseudomonas aeruginosa [18] (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Substituted Tetrahydronaphthalen‐1‐yl‐phenethyl Ureas: Synthesis, Characterization, and Biological Evaluations

2022

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Multi‐target drug discovery is one of the most important objectives in the treatment of carcinogenesis because of the different outcomes of the disease such as bacterial infections due to impaired immune systems. Therefore, a series of new urea derivatives were synthesized to acquire both anti‐proliferative and antimicrobial properties that can be used in chemotherapy. The anti‐cancer and anti‐microbial properties of synthesized urea compounds were investigated on the HeLa cancer line and multiple bacterial strains via using WST‐8 and disc diffusion methods. In anticancer investigations against the HeLa cell line, one synthesized urea derivative exhibited the best activity (IC50: 58.9 μM), which showed up to 8 times less toxic effect (SI: 8.5) against the non‐cancerous human dermal fibroblast (PCS201‐012) cell line. Additionally, some urea derivatives showed antibacterial activities against Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus MRSA with the lowest MIC values. The MIC value obtained against Pseudomonas aeruginosa was at the level of μM for all urea derivatives and was calculated as 7.8125 μM. As a result, some synthesized urea derivatives may be considered as multipotent drug formulations with antibacterial and anticancer properties.

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1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies

Cited by 25 publications

References 22 publications

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

Substituted Tetrahydronaphthalen‐1‐yl‐phenethyl Ureas: Synthesis, Characterization, and Biological Evaluations

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