Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study

Moussa, Ghandoura; Alaaeddine, Rana; Alaeddine, Lynn M.; Nassra, Rasha A.; Belal, Ahmed S.F.; Ismail, Azza; El-Yazbi, Ahmed F.; Abdel‐Ghany, Yasser S.; Hazzaa, A. A. B.

doi:10.1016/j.ejmech.2017.12.065

Cited by 60 publications

(28 citation statements)

References 65 publications

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“…Novel thioquinazolinone-1,2,3-triazole compounds were synthesised using Huisgen azide-alkyne cycloaddition to identify new antiinflammatory agents targeting COX-2 and LOX inhibition. 145 Among them, 116-118 ( Fig. 15) inhibited COX-2 with IC 50 values 0.19, 0.11, and 0.16 µM, respectively while the 15-LOX inhibition analysis showed IC 50 values of 4.33, 7.62, and 5.21 µM, respectively.…”

Section: 23-triazoles As Anti-inflammatory Agentsmentioning

confidence: 97%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

575

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: 23-triazoles As Anti-inflammatory Agentsmentioning

confidence: 97%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

575

289

View full text Add to dashboard Cite

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“…[ 30 ] Therefore, to elucidate the possible interactions of the most active compounds 3f , 3h , 3l , and 3p with either COX‐2 (PDB entry 1CX2) or 5‐LOX (PDB entry 3V99) receptors, a molecular docking study was carried out using Molecular Operating Environment (MOE; version 2008.10) modeling software. [ 26,31 ] Docking scores and binding interactions inside COX‐2 and 5‐LOX active sites are summarized in Table 5.…”

Section: Resultsmentioning

confidence: 99%

“…The docking experiment of the compounds showing the highest selectivity ratio toward COX‐2 enzymes ( 3f , 3h , 3l , and 3p ), as well as SC‐558, and celecoxib, was performed using MOE (10.2008) software (Chemical Computing Group, Montreal, Canada) using the crystal structure of COX‐2 enzyme (PDB entry 1CX2) [ 31 ] and the crystal structure of 5‐LOX enzyme (PDB entry 3V99) [ 47 ] downloaded from the Protein Data Bank (PDB) website (https://www.rcsb.org/). The protein structure was prepared by deleting the repeating chains and water molecules.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and biological evaluation of pyrazolone analogues as potential anti‐inflammatory agents targeting cyclooxygenases and 5‐lipoxygenase

Shabaan

Kamal

Faggal

et al. 2020

Archiv der Pharmazie

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New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5‐lipoxygenase (5‐LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX‐2 selectivity index. Moreover, they showed potent 5‐LOX inhibitory activity relative to celecoxib and zileuton, as positive controls. These promising candidates were further investigated for anti‐inflammatory activity using the carrageenan‐induced rat paw edema method and ulcerogenic liability. The results showed no ulceration, which implies their gastric safety profile. Moreover, these compounds were evaluated for prostaglandin (PGE2) production in rat serum. Molecular docking in the COX‐2 and 5‐LOX active sites was performed to rationalize their anti‐inflammatory activities. Strong binding interactions and effective docking scores were identified. The results indicated that these derivatives are good leads for dual‐acting COX‐2/5‐LOX inhibitors to be used as potent and safe anti‐inflammatory agents.

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“…Quinazolinones and dihydroquinazolinons are important classes of nitrogen-containing heterocycles with an array of biological activities such an antitumor [ 1 , 2 ], anti-inflammatory [ 3 ], antibacterial [ 4 , 5 ], anticonvulsant [ 6 ], etc. As explicit examples, RVX-208 and balaglitazone, structurally based on quinazolin-4(3 H )-one ( Figure 1 ), are now under phase III clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“On-Water” Synthesis of Quinazolinones and Dihydroquinazolinones Starting from o-Bromobenzonitrile

Zibin

Zeng

et al. 2018

Molecules

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A versatile and practical “on-water” protocol was newly developed to synthesize quinazolinones using o-bromobenzonitrile as a novel starting material. Studies have found that air as well as water plays an important role in synthesis of quinazolinones. Further investigation indicated that dihydroquinazolinones can be prepared with this protocol under the protection of N2. The protocol can be extended to other substrates and various quinazolinones and dihydroquinazolinones were obtained. o-Bromobenzamide, o-aminobenzonitrile, and o-aminobenzamide were also evaluated as starting materials, and the results further proved the versatility of this protocol, especially towards dihydroquinazolinones.

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Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study

Cited by 60 publications

References 65 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Synthesis and biological evaluation of pyrazolone analogues as potential anti‐inflammatory agents targeting cyclooxygenases and 5‐lipoxygenase

“On-Water” Synthesis of Quinazolinones and Dihydroquinazolinones Starting from o-Bromobenzonitrile

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