Synthesis and Evaluation of Novel Quinazolinone-1,2,3-Triazoles as Inhibitors of Lipoxygenase

Farjadmand, Fatemeh; Arshadi, Hossein; Moghimi, Setareh; Nadri, Hamid; Moradi, Alireza; Eghtedari, Mohammad; Jafarpour, Farnaz; Mahdavi, Mohammad; Shafiee, Abbas; Foroumadi, Alireza

doi:10.3184/174751916x14558913889738

Cited by 15 publications

(8 citation statements)

References 26 publications

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“…Noting that triazoles can inhibit 5-LO, ~15 triazole compounds were screened, ultimately identifying 5-LOi-3 as a lead inhibitor with an IC 50 value of 33 μM. 188…”

Section: Oxidoreductases (Ec 113 Ec 114)mentioning

confidence: 99%

“…Noting that triazoles can inhibit 5-LO, ∼15 triazole compounds were screened, ultimately identifying 5-LOi-3 as a lead inhibitor with an IC 50 value of 33 μM. 188 The dual inhibition of both the COX and the 5-LO pathways has been another therapeutic goal over the past ∼20 years. Single inhibition of the 5-LO pathway does not totally inhibit the production of proinflammatory prostaglandins in most cells because of the orthogonal COX pathway.…”

Section: Chemical Reviewsmentioning

confidence: 99%

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Targeting Metalloenzymes for Therapeutic Intervention

et al. 2018

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Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in disease and their importance as a class of targets has amplified interest in the development of new strategies to develop inhibitors and ultimately useful drugs. In this Review, we provide a broad overview of several drug discovery efforts focused on metalloenzymes and attempt to map out the current landscape of high-value metalloenzyme targets.

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“…Noting that triazoles can inhibit 5-LO, ~15 triazole compounds were screened, ultimately identifying 5-LOi-3 as a lead inhibitor with an IC 50 value of 33 μM. 188…”

Section: Oxidoreductases (Ec 113 Ec 114)mentioning

confidence: 99%

Section: Chemical Reviewsmentioning

confidence: 99%

Targeting Metalloenzymes for Therapeutic Intervention

et al. 2018

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“…For that reason, many types of research have been conducted in order to find LOX inhibitors. Different organic compounds are reported as LOX inhibitors such as coumarins [ 12 , 13 ], rhodanines [ 14 , 15 ], thiazolidinediones [ 16 ], and quinazolinone-1,2,3-triazoles [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study

et al. 2020

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Lipoxygenases (LOXs) are a family of enzymes found in plants, mammals, and microorganisms. In animals and plants, the enzyme has the capability for the peroxidation of unsaturated fatty acids. Although LOXs participate in the plant defense system, the enzyme’s metabolites can have numerous negative effects on human health. Therefore, many types of research are searching for compounds that can inhibit LOXs. The best quantitative structure–activity relationship (QSAR) model was obtained using a Genetic Algorithm (GA). Molecular docking was performed with iGEMDOCK. The inhibition of lipoxygenase was in the range of 7.1 to 96.6%, and the inhibition of lipid peroxidation was 7.0–91.0%. Among the synthesized compounds, the strongest inhibitor of soybean LOX-3 (96.6%) was found to be 3-benzoyl-7-(benzyloxy)-2H-chromen-2-one. A lipid peroxidation inhibition of 91.0% was achieved with ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate. The docking scores for the soybean LOX-3 and human 5-LOX also indicated that this compound has the best affinity for these LOX enzymes. The best multiple linear QSAR model contains the atom-centered fragment descriptors C-06, RDF035p, and HATS8p. QSAR and molecular docking studies elucidated the structural features important for the enhanced inhibitory activity of the most active compounds, such as the presence of the benzoyl ring at the 3-position of coumarin’s core. Compounds with benzoyl substituents are promising candidates as potent lipoxygenase inhibitors.

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“…This reaction provides an experimentally simple and mild pathway for the formation of carbon‐heteroatom bond, affording triazoles in a single step procedure. In terms of unique properties associated with this type of reaction, many triazole‐containing molecules have been prepared through the simple and efficient click reaction . Taking this into account and the importance of urea and triazole moieties in urease inhibitors, we now report the synthesis and antiurease activity of novel 1‐((1‐substituted benzyl)‐1 H ‐1,2,3‐triazol‐4‐yl)methyl)‐3‐phenyl urea derivatives.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, evaluation, and molecular docking studies of aryl urea‐triazole‐based derivatives as anti‐urease agents

Moghimi

Goli-Garmroodi

Allahyari-Devin

et al. 2018

Archiv der Pharmazie

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Considering the importance of urease inhibitors in the treatment of ureolytic bacterial infections, in this work, the synthesis of novel, aryl urea-triazole-based derivatives as effective urease inhibitors is described. Dichloro-substituted derivative 4o, with IC = 22.81 ± 0.05 μM, is found to be the most potent urease inhibitor, determined by Berthelot colorimetric assay. Docking studies were also carried out for compound 4o to confirm the effective interactions with the urease active site.

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Synthesis and Evaluation of Novel Quinazolinone-1,2,3-Triazoles as Inhibitors of Lipoxygenase

Abstract: This work reports the successful synthesis of quinazolinones carrying triazole derivatives with potent lipoxygenase inhibitory activities. This protocol involves sequential reactions affording novel products in high yields without the need for a tedious work-up procedure.

Cited by 15 publications

References 26 publications

Targeting Metalloenzymes for Therapeutic Intervention

Targeting Metalloenzymes for Therapeutic Intervention

Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study

Synthesis, evaluation, and molecular docking studies of aryl urea‐triazole‐based derivatives as anti‐urease agents

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