Phthalazin-1(2H)-one as a remarkable scaffold in drug discovery

Vila, Noemí; Besada, Pedro; Costas, Tamara; Costas-Lago, Mª Carmen; Terán, Carmen

doi:10.1016/j.ejmech.2014.11.043

Cited by 58 publications

(35 citation statements)

References 172 publications

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“…These muropeptides of bacterial cell envelop can be altered or modified by hydrolases via the action of bacterial glycolytic and peptidolytic enzymes. In some pathogenic bacteria, for example, Streptococcus pneumonia and Listeriamono cytogenes are also conventional for bacteria to deacetylate N ‐acetyl glucosamine residues. Meanwhile, a moderate activity was observed against E .…”

Section: Resultsmentioning

confidence: 99%

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Rizk

Abdelwahab

El‐Badawy

2019

Journal of Heterocyclic Chem

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Phthalazines have received considerable attention for their wide antimicrobial activity. Regiospecific nucleophilic attack of 4‐benzylphthalazin‐1‐ol by the 1‐oxo rather than the aza group on different alkyl halides gave novel phthalazine heterocyclic derivatives. Moreover, a variety of nucleosides bonded to electron‐withdrawing groups were synthesized using 4‐benzylphthalazine‐1‐ol. The density functional theory has been used to investigate the electronic structure of the synthesized compounds. All of the synthesized derivatives showed remarkable activity when tested against Gram‐positive and Gram‐negative bacteria, Aspergillus niger, and Candida albicans. The reactivity of these nucleosides was expected to arise from their bonding with the lone pair of N‐atom of the macromolecules of bacteria. These bonding were expected to inhibit the enzyme by forming highly stable complex with lower highest occupied molecular orbital energy. The structures of these synthesized derivatives were established by Fourier transform infrared, 1H‐NMR, and 13C‐NMR spectroscopic evidence.

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Section: Resultsmentioning

confidence: 99%

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Rizk

Abdelwahab

El‐Badawy

2019

Journal of Heterocyclic Chem

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“…Compound 2 shares the same ring as a central moiety connected to N ‐(3‐aminopropyl)imidazole and cumene. Finally, compound 4 possesses a central 1,2‐dihydro‐1,2,4‐triazole‐3‐thione ring substituted with benzoic acid and phthalazone, which is an important scaffold for drug discovery . Despite their chemical differences, all selected compounds possess polar groups capable of interacting with E‐selectin through hydrogen bonds or electrostatic interactions, hydrophobic moieties that enable van der Waals contacts with the protein receptor, and aromatic rings that can participate in π–π interactions with suitable protein side chains.…”

Section: Resultsmentioning

confidence: 99%

“…Finally,c ompound 4 possesses ac entral 1,2-dihydro-1,2,4-triazole-3-thione ring substituted with benzoica cid and phthalazone, which is an important scaffold for drug discovery. [10] Despite their chemical differences, all selected compounds possess polar groups capable of interacting withE -selectin throughh ydrogen bonds or electrostatic interactions, hydrophobic moieties that enable van der Waals contacts with the protein receptor,a nd aromatic rings that can participate in pp interactions with suitable protein side chains. To elucidate the nature of the bindingi nteractions between the selected set of candidates and the E-selectinr eceptor,M Ds imulations were carriedo ut, as described in the followings ection.…”

Section: Resultsmentioning

confidence: 99%

Discovery of New E‐Selectin Inhibitors by Virtual Screening, Fluorescence Binding Assays, and STD NMR Experiments

et al. 2016

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E-selectin is an endothelial protein that participates in the adhesion of metastatic cancer cells, and is therefore a relevant target for antitumor therapeutic intervention. In this work, virtual screening was used to identify new E-selectin inhibitors from a subset of drug-like molecules retrieved from the ZINC database, including the physiological ligand sLe(x) as reference structure (PDB ID: 1G1T). Four hits were chosen and subjected to molecular dynamics simulations and fluorescence binding assays, which led to the determination of experimental dissociation constants between 333 and 1012 μm. The candidate with the highest affinity was studied by saturation transfer difference (STD) NMR experiments and complete relaxation and conformational exchange matrix analysis of saturation transfer (CORCEMA-ST), aimed at identifying the preferable binding mode with E-selectin. Our results revealed that this new inhibitor binds more strongly than sLe(x) in the E-selectin binding site, in good agreement with simulation predictions. These properties will prove valuable for the future design of drugs that target E-selectin.

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“…Finally, in order to highlight the synthetic potential of this new strategy, selected transformations of the generated ethyl 2‐(4‐phenyl‐1H‐pyrrole‐3‐carbonyl)benzoate ( 4 a ) were conducted (Scheme ). Treatment of 4 a with hydrazine hydrate in EtOH under reflux condition underwent cyclization to provide bio‐active pyrrolinyl substituted phthalazinone 6 in 81% (Scheme ) …”

Section: Figurementioning

confidence: 99%

′′One‐Pot′′ Selective Synthesis of 3,4‐Disubstituted Pyrroles and Benzo[f]indole‐4,9‐diones from 1,3‐Indanedione, Aromatic Aldehydes and TosMIC

et al. 2017

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A variety of 3,4‐disubstituted pyrroles and benzo[f]indole‐4,9‐diones have been selectively synthesized from readily available aromatic aldehydes, 1,3‐Indanedione and tosylmethyl isocyanide (TosMIC) by a one‐pot procedure in high yields. This methodology features operationally simple, practical with broad substrate scope and usage of easy to handle reagents. The one‐pot sequential reactions proposed to proceeds through a tandem in situ generated chalcones and [3+2]‐cycloaddition/ring cleavage or expansion process.

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Phthalazin-1(2H)-one as a remarkable scaffold in drug discovery

Cited by 58 publications

References 172 publications

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Discovery of New E‐Selectin Inhibitors by Virtual Screening, Fluorescence Binding Assays, and STD NMR Experiments

′′One‐Pot′′ Selective Synthesis of 3,4‐Disubstituted Pyrroles and Benzo[f]indole‐4,9‐diones from 1,3‐Indanedione, Aromatic Aldehydes and TosMIC

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