Robust therapeutic potential of carbazole-triazine hybrids as a new class of urease inhibitors: A distinctive combination of nitrogen-containing heterocycles

Ibrar, Aliya; Kazmi, Madiha; Khan, Ajmal; Halim, Sobia Ahsan; Saeed, Aamer; Mehsud, Saifullah; Al‐Harrasi, Ahmed; Khan, Imtiaz

doi:10.1016/j.bioorg.2019.103479

Cited by 21 publications

(7 citation statements)

References 70 publications

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Section: Resultsmentioning

confidence: 99%

“…It has recently been reported that the electron pulling effects of nitro group and/or presence of moderate halogenated substitutions could possibly improve the activity of urease inhibitors. [32,33] Initially, some previously designed derivatives (4 a--4 e) were planned to test against urease and these compounds have executed good to excellent activity results. Among these, compound 4 d, a nitro substituted molecule, was stand out to be the best inhibitor (IC 50 = 21.6 � 0.003 μM) that also signified towards the probable contribution of electron deficient functional groups towards inhibition.…”

Section: Urease Inhibition Evaluationmentioning

confidence: 99%

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Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para-toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a-4 l) were found active against the studied enzyme in comparison with the standard drug thiourea (IC 50 = 21.26 � 0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta-nitro substituted 4 k with IC 50 = 0.7 � 0.002 μM and a para-nitro containing compound 4 l with IC 50 = 1.0 � 0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π-stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease.

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Section: Resultsmentioning

confidence: 99%

Section: Urease Inhibition Evaluationmentioning

confidence: 99%

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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“…90 Kojic acid was used as a reference standard inhibitor to compare the tyrosinase activity of compounds. Urease inhibitory activity was determined by measuring ammonia production using the indophenol method as described previously 93,94 and thiourea was used as positive control.…”

Section: Synthesis Of Nitrogen-containing Chalconesmentioning

confidence: 99%

Chalcones bearing nitrogen‐containing heterocyclics as multi‐targeted inhibitors: Design, synthesis, biological evaluation and molecular docking studies

Sıcak

Kekeçmuhammed

Karaküçük‐İyidoğan

et al. 2023

J of Molecular Recognition

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In this work, a series of chalcones (1a–d, 2a–d, 3a–d, 4a–d, and 5a–d) were designed and synthesized by Claisen–Schmidt condensation. Also, their chemical structures were elucidated using UV–Vis, FT IR, 1H NMR, 13C NMR, MS spectral data, and elemental analyses. Subsequently, the anticholinesterase, tyrosinase, urease inhibitory activities and antioxidant activities of all chalcones were evaluated. The inhibitory potential of all chalcones in terms of IC50 value was observed to range from 7.18 ± 0.43 to 29.62 ± 0.30 μM against BChE by comparing with Galantamine (IC50 46.06 ± 0.10 μM) as a reference drug. Also, compounds 2c, 3c, 4c, 4b, and 4d exhibited high anticholinesterase activity against both AChE and BChE enzymes. The tyrosinase inhibitory activity results revealed that three compounds (IC50 1.75 ± 0.83 μM for 2b, IC50 2.24 ± 0.11 μM for 3b, and IC50 1.90 ± 0.64 μM for 4b) displayed good inhibitory activity against tyrosinase compared with kojic acid (IC50 0.64 ± 0.12 μM). In addition, other different three chalcones (IC50 22.34 ± 0.25 μM for 2c, IC50 20.98 ± 0.08 μM for 3c, and IC50 18.26 ± 0.13 μM for 4c) showed excellent inhibitory activity against the urease by comparing with thiourea (IC50 23.08 ± 0.19 μM). Compounds 3c and 4c showed the best potency in all antioxidant activity tests. In light of these findings, the structure–activity relationship for compounds was also described. Furthermore, molecular modeling studies, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacophore analyses of compounds, gave important information about the interactions and drug‐likeness properties. As a result, all chalcones exhibited suitable ADMET findings, predicting good oral bioavailability.

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“…[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. [30][31][32][33][34][35] It is documented that some of the 1,3,4 oxadiazoles derived Mannich bases decrease inflammation and prevent fungal growth and they also possess analgesic, antiulcer, antibacterial, anti-HIV, anti-convulsant, anti-tuberculosis and anticancer activities and as inhibitors of various other enzymes and are used in many other applications.…”

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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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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Robust therapeutic potential of carbazole-triazine hybrids as a new class of urease inhibitors: A distinctive combination of nitrogen-containing heterocycles

Cited by 21 publications

References 70 publications

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Chalcones bearing nitrogen‐containing heterocyclics as multi‐targeted inhibitors: Design, synthesis, biological evaluation and molecular docking studies

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

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