Synthesis, in vitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole, thiadiazole and thiosemicarbazide functionalities

Menteşe, Emre; Akyüz, Gülay; Emirik, Mustafa; Baltaş, Nimet

doi:10.1016/j.bioorg.2018.10.031

Cited by 40 publications

(32 citation statements)

References 43 publications

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“…[16,17] Many nitrogen atom containing azolic templates have recently been reported as antiurease agents as well. Norfloxacin hybrids, [18] conazole analogue, [19] benzimidazole derivatives, [20] thiazole derivative, [21] azol-β-lactam, [22] benzisoelenazolone, [23] urea-triazole conjugate, [24] thiadiazole derivative [25] are some of the crucial examples ( Figure 1).…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…For residues within 5 Å of the ligand, Prime refinement was used. Glide redocking was carried out for structures within 30 kcal/mol of the best poses (Menteşe et al, 2019;€ Ozil et al, 2020). The binding affinity was determined and ranked based on the docking score.…”

Section: The Protocol Of Docking Studymentioning

confidence: 99%

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study

Emirik

2020

Journal of Biomolecular Structure and Dynamics

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Inspired by the 'There is no scientific evidence that turmeric prevents COVID-19' statement made by WHO, the protective or therapeutic potential of the compounds in turmeric contents was investigated against COVID-19 with in silico methodology. The drugs used for experimental COVID-19 therapies were included in this study using the same method for comparison with turmeric components. The 30 turmeric compounds and nine drugs were performed in the docking procedure for vital proteins of COVID-19. With evaluations based on docking scores, the Prime MMGBSA binding free energy and protein-ligand interactions were identified in detail. The 100 ns MD simulations were also performed to assess the stability of the ligands at the binding site of the target proteins. The Root Mean Square Deviation (RMSD) is used to obtain the average displacement for a particular frame concerning a reference frame. The results of this study are suggesting that turmeric spice have a potential to inhibit the SARS-CoV-2 vital proteins and can be use a therapeutic or protective agent against SARS-CoV-2 via inhibiting key protein of the SARS-CoV-2 virus. The compound 4, 23 and 6 are the most prominent inhibitor for the main protease, the spike glycoprotein and RNA polymerase of virus, respectively. The MD simulation validated the stability of ligand-protein interactions. The compactness of the complexes was shown using a radius of gyration. ADME properties of featured compounds are in range of 95% drug molecules. It is hoped that the outputs of this study will contribute to the struggle of humanity with COVID-19.

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“…Although different candidates are in various phases of discovery and development pipeline [17][18][19][20], no drugs with novel skeleton against H. pylori have been approved recently. Compound 1c with unique skeleton exhibited most the promising potency against H. pylori compared with PMT, and was selected as the representative compound for further investigation.…”

Section: Pharmacological Evaluationmentioning

confidence: 99%

“…H. pylori creates a local neutral environment for survival by continuously releasing ammonia into succus gastricus, mediated by its own urease. Therefore, urease plays an essential role for H. pylori colonization in the human stomach, and is considered to be a critical target in the exploitation of anti-H. pylori agents [17][18][19][20]. Until now, no drug has been approved by Food and Drug Administration (FDA) targeting H. pylori urease [20,21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against Helicobacter pylori

et al. 2020

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Taking palmatine (PMT) as the lead, 20 new PMT derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole (MTZ)-resistant Helicobacter pylori (H. pylori) strains. The structure–activity relationship (SAR) indicated that the introduction of a suitable secondary amine substituent at the 9-position might be beneficial for potency. Among them, compound 1c exhibited the most potent activities against MTZ-resistant strains, with minimum inhibitory concentration (MIC) values of 4–16 μg/mL, better than that of the lead. It also exhibited a good safety profile with a half-lethal dose (LD50) of over 1000 mg/kg. Meanwhile, 1c might exert its antimicrobial activity through targeting H. pylori urease. These results suggested that PMT derivatives might be a new family of anti-H. pylori components.

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Synthesis, in vitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole, thiadiazole and thiosemicarbazide functionalities

Cited by 40 publications

References 43 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

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study

Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against Helicobacter pylori

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