3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation

Shi, Wei-Kang; Deng, Rui-Cheng; Wang, Pengfei; Yue, Qin-Qin; Liu, Qi; Ding, Kun-Ling; Yang, Mei‐Hui; Zhang, Hongyu; Gong, Si-Hua; Deng, Min; Liu, Wen-Run; Qian, Feng; Xiao, Zhu‐Ping; Zhu, Hai‐Liang

doi:10.1016/j.bmc.2016.07.052

Cited by 50 publications

(9 citation statements)

References 41 publications

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“…Because of the well-known chelating properties and antiurease potential of hydroxamic acids, in 2013 and 2016, Xiao et al and Shi et al, respectively, synthesized a large series of derivatives with different groups at positions 2, 3 and 4 of the benzene ring ( Scheme 59 ). Both studies reported remarkable results for urease inhibitory activity, including very low IC 50 values for some of the tested title compounds [188] , [189] . As shown in the SAR studies, the hydrophobic behavior of the substituent is important to increase the inhibitory activity, although bulky hydrophobic groups reduce the potency.…”

Section: Organic Substances As Urease Inhibitorsmentioning

confidence: 99%

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

Rego

Queiroz

Brito

et al. 2018

Journal of Advanced Research

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Section: Organic Substances As Urease Inhibitorsmentioning

confidence: 99%

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

Rego

Queiroz

Brito

et al. 2018

Journal of Advanced Research

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“…Hydroxamic acids have been the best recognized urease inhibitors, and they have been widely used as a reference urease inhibitor for the development of novel urease inhibitors [ 19 ]. It is the only commercially available medical urease inhibitor with an IC 50 value of 18.2 μM against H. pylori urease [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Urease Inhibitor of Ruminal Microbiota Screened through Molecular Docking

Zhang

et al. 2020

IJMS

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Inhibition of the urease activity of ruminal microbiota is not only beneficial for increasing dietary and endogenic urea-N utilization efficiency in ruminants but also might be applicable for the preservation of nitrogen fertilizer in soil and treatment of gastrointestinal and urinary tract infections caused by ureolytic bacteria. To discover urease inhibitors to efficiently target ruminal microbiota, the identified ruminal microbial metagenomic urease gene was used to construct a homology model to virtually screen urease inhibitors from the ChemDiv database by molecular docking. The GMQE and QMEAN values of the homology model were 0.85 and −0.37, respectively, indicating a good model quality. The inhibition effect of the screened urease inhibitor for ruminal urea degradation was assessed by ruminal microbial fermentation in vitro. The toxic effect of the candidate inhibitor was performed using gut Caco-2 cells in vitro. The results showed that compound 3-[1-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-1H-pyrrol-2-yl] propanoic acid (ChemDiv_ID: 6238-0047, IC50 = 65.86 μM) was found to be the most effective urease inhibitor among the candidate compounds. Compound 6238-0047 significantly lowered the amount of urea degradation and ammonia production in ruminal microbial fermentation. The 24 h degradation rate of compound 6238-0047 in ruminal microbial fermentation was 3.32%–16.00%. In addition, compound 6238-0047 (10–100 μM) had no significant adverse effect on the cell viability of Caco-2 cells. Molecular docking showed that compound 6238-0047 could interact with Asp359 in the active site and Cys318 in the flap region by the hydrogen bond and Pi-Alkyl interaction, respectively. Compound 6238-0047 could be used as a novel inhibitor for decreasing the urease activity of ruminal microbiota.

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“…The antibiotics administered, usually act on the bacterium, on the other hand inactivation of urease enzyme is not yet totally exploited. At present Palmatine, Bis (N-methylaminomethyl) phosphinic acid, and some derivatives of 3-Arylpropionylhydroxamic acid, pyrogallol and catechol were observed to suppress urease by acting on active site [11][12][13][14]. Acetohydroxamic acid (AHA), which is used to treating H. pylori by inhibiting urease enzyme, also exhibits severe side effects [15].…”

Section: Current Therapeutics Against H Pylorimentioning

confidence: 99%

Urease: The Ultimate Therapeutic Target for Helicobacter Pylori

Keya¹

2018

IJCSMB

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Gastric ulcer and carcinoma is quite frequent throughout the globe. The most prevalent causative agent of gastric ulcer and carcinoma is a gram-negative bacterium, Helicobacter pylori (H. pylori). The ineffectiveness and side effects of approved drugs as well as antibiotic resistance is a major problem in the treatment of H. pylori. H. pylori possess uncommon urease enzyme which catalyzes the hydrolysis of urea. Urease is necessary for colonization of H. Pylori in the gastric mucosa and is a potent immunogen that elicits a vigorous immune response. As urease acts as both colonization and virulence factor, new inhibitor of urease from plant sources with no/less adverse effect is vital to efface H. pylori.

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3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation

Cited by 50 publications

References 41 publications

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

A Novel Urease Inhibitor of Ruminal Microbiota Screened through Molecular Docking

Urease: The Ultimate Therapeutic Target for Helicobacter Pylori

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