Synthesis, molecular docking, and biological evaluation of nitroimidazole derivatives as potent urease inhibitors

Talebi, Meysam; Hamidian, Elham; Niasari-Naslaji, Fatemeh; Rahmani, Sogand; Hosseini, Faezeh Sadat; Boumi, Shahin; Montazer, Mohammad Nazari; Asadi, Mehdi; Amanlou, Massoud

doi:10.1007/s00044-021-02727-4

Cited by 18 publications

(3 citation statements)

References 39 publications

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“…[13,14] The classification of ureases has been done in two different groups (i) active-site-directed inhibitors (substrate-like) such as hydroxamic and hydroxyurea (ii) mechanism-based-directed inhibitors, for instance, imidazoles and phosphorodiamidates. [15] Recently, several classes of compounds including hydroxamic acids, [16,17] phosphoramidites, [18] boronic and boric acids, [19] quinones, [20,21] heavy metal ions, [22] imidazoles, [23] and others have been investigated as urease inhibitors. [24][25][26][27][28][29][30] The bacterial ureases can also be inhibited by the five-membered heterocycles like 1,2,4 triazoles and 1,3,4 oxadiazoles.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, several classes of compounds including hydroxamic acids, [16,17] phosphoramidites, [18] boronic and boric acids, [19] quinones, [20,21] heavy metal ions, [22] imidazoles, [23] and others have been investigated as urease inhibitors [24–30] . The bacterial ureases can also be inhibited by the five‐membered heterocycles like 1,2,4 triazoles and 1,3,4 oxadiazoles [30–35] .…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors

Mutahir

Khan

Almehizia

et al. 2023

Chemistry & Biodiversity

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Mannich bases consisting of 1,3,4‐oxadiazole‐2‐thione (3 a–3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4‐chlorophenyl (−R) and 4‐hydroxyphenyl (−R′) was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which −R was phenyl and −R′ was isopropyl group. However, when both −R and −R′ were either 4‐chlorophenyl groups (3 l) or only −R′ was 4‐nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data‐supported in‐vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO‐LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors

Mutahir

Khan

Almehizia

et al. 2023

Chemistry & Biodiversity

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“…To date, various types of urease inhibitors have been reported, including nitroimidazole, coumarin and polyphenol derivatives (Figure 1). [5][6][7][8][9][10][11] However, many of these compounds failed to enter the clinical trial due to certain serious side effects or high toxicity. Acetohydroxamic acid (AHA), one of the few FDA-approved urease inhibitors, is prescribed for the treatment and prevention of infectious urinary calculi [12] Although with clear urease inhibitory effect, adverse effects such as headache, nausea, itchy skin often caused discontinuation of therapy.…”

Section: Introductionmentioning

confidence: 99%

Development of Urease Inhibitors by Fragment‐Based Dynamic Combinatorial Chemistry

et al. 2022

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In this study, fragment-based dynamic combinatorial chemistry (DCC) was explored for the development of novel urease inhibitors. Based on a rationally designed fragment, two iteratively evolved dynamic combinatorial libraries (DCLs) were generated and screened in the presence of urease template.The best ligand identified revealed not only strong urease inhibition but also low cytotoxicity. Additionally, a possible inhibitory mechanism was elucidated in the binding kinetics study and docking simulation.

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Methimazole Analogs as Urease Inhibitors: Synthesis, In Silico and In Vitro Evaluation

Çapan

2022

ChemistrySelect

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Urease plays a key role in urinary tract and gastrointestinal infections for which inhibition of it could prove to be substantial as a potential therapeutic option. Here, synthesized thirty novel compounds in four different series based on methimazole skeleton, also known as thiamazole, a drug that is used for the treatment of hyperthyroidism. Characterization of novel compounds consisting oxadiazoles, hydrazine-1-carbothioamides and N'-arylidenebenzohydrazides were performed by 1 H-, 13 C-NMR and high resolution mass spectrometry (HRMS).The synthesized molecules were examined for structure-activity relationship in urease inhibition and found to exhibit inhibitory potency in a range of IC50 = 3.56-14.08 μM compared to urea and acetohydroxamic acid used as standard. Moreover, molecular docking was performed to understand ligand binding interactions in the active site of the enzyme (Jack bean urease, Protein Data Bank ID 3LA4). The promise of addressing urinary tract and gastrointestinal disorders through urease inhibition is discussed.

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Synthesis, molecular docking, and biological evaluation of nitroimidazole derivatives as potent urease inhibitors

Cited by 18 publications

References 39 publications

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors

Development of Urease Inhibitors by Fragment‐Based Dynamic Combinatorial Chemistry

Methimazole Analogs as Urease Inhibitors: Synthesis, In Silico and In Vitro Evaluation

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