Synthesis and Evaluation of Novel Pyrido[1,2-b][1,2,4]triazine-2,6-dione and Pyrido[1,2-b][1,2,4]triazepine-2,7-dione Derivatives as Antioxidant Agents

Serrar, H.; Marmouzi, Ilias; Benzekri, Zakaria; Boukhris, Saı̈d; Hassikou, Amina; Faouzi, My El Abbés; Souizi, Abdelaziz

doi:10.2174/1570178614666170227124523

Cited by 15 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter product was converted to furo [2,3-d] Numerous pharmacological, therapeutic, and biological properties of 1,2,4-triazepines have been discovered. [26,27] Additionally, we have already discussed the biological significance and synthesis of 1,2,4-triazepine molecules. [28] Therefore, our goal was to create novel heterocycles incorporate triazepine rings.…”

Section: Resultsmentioning

confidence: 99%

Novel Furan and Furo[2,3–d]pyrimidinone Analogues: Cytotoxicity, Antioxidant, and Bleomycin‐Dependent DNA Damage Assessment

Musbah,

Mohammed,

El‐Mekabaty

2023

ChemistrySelect

View full text Add to dashboard Cite

Ethyl 2‐amino‐4,5‐diphenylfuran‐3‐carboxylate (2), a reactive synthon, was successfully used to synthesize a novel series of furan and furo[2,3–d]pyrimidinone analogues by interactions with the proper chemical reagents. With the aid of precise spectroscopic data (FT‐IR, Mass, 1H‐NMR, and 13C‐NMR spectra), the structures of products were clearly established. The cytotoxic results by MTT assay showed that furo[2,3–d]pyrimidinone analogues 4 (IC50=6.1±0.8 & 10.2±2.5 μM), 6 (IC50=9.2±2.1 & 17.8±0.5 μM), 11 (IC50=7.1±0.5 & 9.2±1.8 μM), 12 (IC50=5.4±2.3 & 9.8±1.7 μM), 15 (IC50=5.2±2.0 & 8.8±2.0 μM), 18 (IC50=4.2±2.4 & 10.7±1.8 μM), and 21 (IC50=12.8±1.9 & 18.8±0.9 μM) had strong in vitro cytotoxic activities to inhibit the growth of colorectal carcinoma (HCT‐116), and prostate cancer (PC3) cell lines, respectively. However, their effects on normal lung fibroblast (WI‐38) were weak in comparison to 5‐fluorouracil as a positive control. On the other hand, the biological evaluations supported the presence of strong antioxidant activity for the furo[2,3–d]pyrimidinone analogues 4, 6, 15, 17, and 21 (% inhibition=89.10, 84.16, 82.09, 88.11, and 80.23 %, respectively) when compared to ascorbic acid (88.42 %). It has been proven that the most powerful cytotoxic and antioxidant compounds have a superior protective influence on DNA against bleomycin‐induced damage.

show abstract

Section: Resultsmentioning

confidence: 99%

Novel Furan and Furo[2,3–d]pyrimidinone Analogues: Cytotoxicity, Antioxidant, and Bleomycin‐Dependent DNA Damage Assessment

Musbah,

Mohammed,

El‐Mekabaty

2023

ChemistrySelect

View full text Add to dashboard Cite

show abstract

“…), 2225 (C≡N), 1750, 1670 (2C=O), 1600 (C=N). 1 [1,2,4,5]tetrazine-6-carbonitrile (9). Orange crystals are obtained; yield (85) %, mp.…”

Section: -Methyl-2-oxo-1-((2-oxopropyl)amino)-6-phenyl-12-dihydropyri...mentioning

confidence: 99%

“…Heterocyclic compounds containing the pyridine 1 nucleus show a wide range of interesting biological effects, such as anticancer 2 – 4 , antioxidant 5 , 6 , antimicrobial 2 , 6 , 7 , and anti-viral 8 . Furthermore, it has been demonstrated that 1,2,4-triazepines have a wide spectrum of therapeutic and biological effects 9 – 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the molecular docking investigations on Janus Kinase-2 (PDB ID: 4P7E) were carried out to study the binding mechanism, binding affinity, and non-bonding contacts.Heterocyclic compounds containing the pyridine 1 nucleus show a wide range of interesting biological effects, such as anticancer 2-4 , antioxidant 5,6 , antimicrobial 2,6,7 , and anti-viral 8 . Furthermore, it has been demonstrated that 1,2,4-triazepines have a wide spectrum of therapeutic and biological effects [9][10][11] .Moreover, 1,2,4,5-tetrazines are a family of heterocyclic compounds having a diverse variety of biological actions, including anticonvulsant, anti-inflammatory, and antibacterial properties 12 . Many studies have shown that several 1,2,4,5-tetrazine compounds exhibit anticancer activity [13][14][15] .Tetrazepines are seven-membered azaheterocyclic molecules with valuable medical and pesticide applications 16 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of pyrido-annelated [1,2,4,5]tetrazines, [1,2,4]triazepine, and [1,2,4,5]tetrazepines for anticancer, DFT, and molecular docking studies

Hassan

Nabil

El‐Sebaey

et al. 2023

Sci Rep

View full text Add to dashboard Cite

In this strategy, we attempt to design various novel nitrogen-rich heterocycles in one molecule. Green, simple, and efficient aza-annulations of an active, versatile building block, 1-amino-4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (1), with different bifunctional reagents were developed under solvent-free conditions, resulting in the bridgehead tetrazines and azepines (triazepine and tetrazepines). Pyrido[1,2,4,5]tetrazines have been synthesized through two pathways; [3 + 3]- and [5 + 1]-annulations. In addition, pyrido-azepines have been developed by applying [4 + 3]-and [5 + 2]-annulations. This protocol establishes an efficient technique for synthesizing essential biological derivatives of 1,2,4,5-tetrazines, 1,2,4-triazepines, and 1,2,4,5-tetrazepine, tolerating a diverse variety of functionalities without the need for catalysis and fast reaction rates in high yields. The National Cancer Institute (NCI, Bethesda, USA) examined twelve compounds produced at a single high dosage (10−5 M). Compounds 4, 8, and 9 were discovered to have potent anticancer action against certain cancer cell types. To explain NCI results, the density of states was calculated to conduct a better description of the FMOs. The molecular electrostatic potential maps were created to explain a molecule's chemical reactivity. In silico ADME experiments were performed to better understand their pharmacokinetic characteristics. Finally, the molecular docking investigations on Janus Kinase-2 (PDB ID: 4P7E) were carried out to study the binding mechanism, binding affinity, and non-bonding contacts.

show abstract

“…Fused heterocycles containing nitrogen are distinctive building blocks because they are the primary motifs for many natural products and efficiently incorporated in a broad range of heterocyclic compounds that have a significant pharmaceutical effect. − As such, these ring systems are often considered as important pillars for the design and development of new pharmaceutically active molecules and drugs. , Pyrido-triazine derivatives and their analogy are among these significant heterocycles, which have shown distinct and diverse biological activities such as anticancer, anti-avian influenza virus (H5N1), antioxidant, antibacterial, , antifungal, antimicrobial, and antiviral functions. Moreover, some examples of this class of compounds can act as sirtuin modulators, HIV integrase inhibitors, and antagonists of the histamine H3 receptor .…”

Section: Introductionmentioning

confidence: 99%

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1′,2′:2,3][1,2,4]triazino[5,6-b]indole Derivatives

Ibrahim

Behbehani

2021

ACS Omega

View full text Add to dashboard Cite

An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido-[1,2-b][1,2,4]triazine and pyrido[1′,2′:2,3][1,2,4]triazino[5,6-b]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under highpressure conditions. In addition, trifluoroacetic acid was used to induce this transformation. In this research, conducting the targeted reactions under high pressure using the Q-tube reactor was found to be superb in comparison to that under the traditional refluxing conditions. X-ray single-crystal analysis was utilized in this study to authenticate the structure of the synthesized products.

show abstract

Synthesis and Evaluation of Novel Pyrido[1,2-b][1,2,4]triazine-2,6-dione and Pyrido[1,2-b][1,2,4]triazepine-2,7-dione Derivatives as Antioxidant Agents

Cited by 15 publications

References 0 publications

Novel Furan and Furo[2,3–d]pyrimidinone Analogues: Cytotoxicity, Antioxidant, and Bleomycin‐Dependent DNA Damage Assessment

Novel Furan and Furo[2,3–d]pyrimidinone Analogues: Cytotoxicity, Antioxidant, and Bleomycin‐Dependent DNA Damage Assessment

Synthesis of pyrido-annelated [1,2,4,5]tetrazines, [1,2,4]triazepine, and [1,2,4,5]tetrazepines for anticancer, DFT, and molecular docking studies

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1′,2′:2,3][1,2,4]triazino[5,6-b]indole Derivatives

Contact Info

Product

Resources

About