Synthesis, biological evaluation and structure–activity relationships of new phthalazinedione derivatives with vasorelaxant activity

Munín, Javier; Quezada, Elías; Cuíñas, Andrea; Campos‐Toimil, Manuel; Uriarte, Eugenio; Santana, Lourdes; Viña, Dolores

doi:10.1016/j.ejmech.2014.05.052

Cited by 14 publications

(7 citation statements)

References 49 publications

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“…Some 2-benzylidene-1-indanone derivatives have anti-inflammatory effects against acute lung injury [33]. Synthesized 1,4-Phthalazinedione derivatives are found to display a vasorelaxant activity [34] and antibacterial activity [35]. We synthesized Ziziphus spina-christi (Jujube) root-loaded silver oxide nanoparticles (ZS-Ag-NPs) with a minimal nanometer size and uniform dispersion, which was confirmed by Zetasizer, TEM, FT-IR, and XRD pattern analyses.…”

Section: Discussionmentioning

confidence: 76%

“…For instance, indole-3-carboxylic acid, 5-methoxy-2-methyl-1-(3-methylphenyl)-, ethyl ester, Kaempferol (flavonol), Cannabinol (3.41% of the total peak area), 3,3-Diphenyl-1-indanone and 1,4-Phthalazinedione, 2,3-dihydro-6-nitro-, phenol, 2,2 -methylenebis[6-(1,1-dimethylethyl)-4-methyl (5.22% of the total peak area), and undecane (5.15% of the total peak area) (Table 1, Figure S1). Derivatives have vasorelaxant activity [34] and antibacterial activity [35].…”

Section: Gc-ms Analysis Of Ziziphus Spina-christi Root Methanol Extractmentioning

confidence: 99%

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Synthesis of Ziziphus spina-christi (Jujube) Root Methanol Extract Loaded Functionalized Silver Nanoparticle (ZS-Ag-NPs); Physiochemical Characterization and Effect of ZS-Ag-NPs on Adipocyte Maturation, Adipokine and Vascular Smooth Muscle Cell Interaction

et al. 2021

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In this research, a simple, green approach was employed to synthesize silver nanoparticles with the aid of Ziziphus spina-christi (L.) methanol root extract, which can act as a reducing, capping agent to treat obesity and inflammation. Globally, Ziziphus spina-christi (Jujube) root is used in traditional therapy as a lipolysis promoter. GC-MS results confirmed the availability of kaempferol (flavonol), cannabinol and indole-3-carboxylic acid in Ziziphus spina-christi root methanol extract (ZSE). ZSE silver nanoparticles (ZS-Ag-NPs) were synthesized and their effect on mitochondrial fatty acid oxidation capacity and adipokine levels in maturing adipocytes were analyzed. Maturing adipocytes treated with 0.4 µg/dL of ZSE and ZS-Ag-NPs significantly reduced the lipid content in adipocytes by 64% and 82%, respectively. In addition, lipolysis-related genes such as LPL (1.9 fold), HSL (2.3 fold), PGC-1α (3 fold), UCP-1 (4.1 fold), PRDM16 (2 fold) and PPARα (2.7 fold) increased significantly in ZS-Ag-NPs treated maturing adipocytes. The ZS-Ag-NPs treatment significantly decreased insulin resistance and metabolic inflammation-related LTB4-R, TNF-α, IL-4 and STAT-6 mRNA levels. Mitochondrial thermogenesis stimulating capacity of ZS-Ag-NPs was further confirmed by the significantly enhanced CREB-1 and AMPK protein levels in adipocytes. Furthermore, ZS-Ag-NPs treated adipokines (condition media, CM) were treated with human umbilical vein endothelial cells (HUVECs) to determine cytotoxicity and pro-inflammatory stimulus capacity. We found that ZS-Ag-NPs treated adipocyte CM effectively increased mRNA expression levels of the vascular endothelial cell growth factor (VEGF), and down-regulated oxidative stress (LPO, eNOS, and HO) and vascular cell inflammation (ICAM, VCAM, TNF-α, IL-1β, and NF-κB). In conclusion, ZS-Ag-NPs displayed an action at the molecular level in mitochondrial fatty acid oxidation, decreased adipokine secretion in adipocytes, and enhanced vascular endothelial cell growth. This molecular mechanical action of ZS-Ag-NPs reduced effectively obesity progressions and metabolic inflammatory pathogenesis associated with aging.

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Section: Discussionmentioning

confidence: 76%

Section: Gc-ms Analysis Of Ziziphus Spina-christi Root Methanol Extractmentioning

confidence: 99%

Synthesis of Ziziphus spina-christi (Jujube) Root Methanol Extract Loaded Functionalized Silver Nanoparticle (ZS-Ag-NPs); Physiochemical Characterization and Effect of ZS-Ag-NPs on Adipocyte Maturation, Adipokine and Vascular Smooth Muscle Cell Interaction

et al. 2021

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“…In our study, the cytotoxic effects among six concentrations (5–100 μM) of compounds 14c on mouse aortic vascular smooth muscle (MOVAS) were assessed and studied by cell counting kit‐8 (CCK8) ( n = 5). (Munin et al, 2014) As depicted in Figure 6f, after 24 h co‐incubation with MOVAS cells, compound 14c (more than 25.0 μM) decreased the viability of MOVAS cells and with the increase of concentration, the cytotoxicity increased. However, for a lower concentration (5–25 μM), compound 14c was well tolerated by the cells.…”

Section: Resultsmentioning

confidence: 86%

Design, synthesis, and biological evaluation of novel NO‐releasing 4‐chromanone derivatives as potential vasodilator agents

et al. 2022

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The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway is an effective mechanism involved in the treatment of hypertension. In our search for potential antihypertensive agents, a series of novel NO‐donor derivatives of the 4‐chromanone skeleton were designed and synthesized by coupling furoxans or nitrooxy NO‐donor moieties. All derivatives showed enhanced nitric oxide releasing capacity and vasodilator activity with EC50 values ranging from 0.0215 μM to 1.46 μM, obviously superior to those of precursor 3. These biological evaluations indicated that all compounds displayed an important vasorelaxant effect, and several compounds (9c, 14b, 14c, 14d) presented good vasodilator activity, with 14c being the best. Furthermore, molecular modeling studies revealed that compound 14c occupied the pocket well with the phosphodiesterase 5 domain in a favorable conformation. In conclusion, we observed that these novel compounds can act as structural templates for the design and subsequent development of new vasodilators and antihypertensive drugs.

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“…9 Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as antimicrobial, [10][11][12] antidiabetic, 13 analgesic, 14,15 anticonvulsant, 16,17 antitumor, [18][19][20] antiproliferative, 20 antiepileptic, 21,22 anti-inflammatory, 23,24 and vasorelaxant. 25,26 In addition, phthalazines are known as serotonin reuptake inhibitors and are considered as anti-depression agents. 27 Also, they are crucial precursors in the synthesis of many compounds with interesting pharmacological properties like phosphodiesterase inhibitors and blood platelet aggregation inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Phthalazines and phthalazine hybrids as antimicrobial agents: Synthesis and biological evaluation

Mourad

Makhlouf

Soliman

et al. 2019

Journal of Chemical Research

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Phthalazine and phthalazinone derivatives are important owing to their significant biological activities and pharmacological properties. Herein, a benzoic acid derivative (2), a benzoxazin-1-one derivative (3), and an oxophthalazin-2(1 H)-yl)acetohydrazide (13) are utilized as precursors to construct a novel series of phthalazinones bearing various valuable functional groups in excellent yields via several simple and promising approaches. Finally, the antimicrobial activity of the newly synthesized phthalazines is screened against different microbial strains; namely, Gram-negative and Gram-positive bacteria utilizing Amoxicillin as a standard drug.

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Synthesis, biological evaluation and structure–activity relationships of new phthalazinedione derivatives with vasorelaxant activity

Cited by 14 publications

References 49 publications

Synthesis of Ziziphus spina-christi (Jujube) Root Methanol Extract Loaded Functionalized Silver Nanoparticle (ZS-Ag-NPs); Physiochemical Characterization and Effect of ZS-Ag-NPs on Adipocyte Maturation, Adipokine and Vascular Smooth Muscle Cell Interaction

Synthesis of Ziziphus spina-christi (Jujube) Root Methanol Extract Loaded Functionalized Silver Nanoparticle (ZS-Ag-NPs); Physiochemical Characterization and Effect of ZS-Ag-NPs on Adipocyte Maturation, Adipokine and Vascular Smooth Muscle Cell Interaction

Design, synthesis, and biological evaluation of novel NO‐releasing 4‐chromanone derivatives as potential vasodilator agents

Phthalazines and phthalazine hybrids as antimicrobial agents: Synthesis and biological evaluation

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