Synthesis and QSAR analysis of chalcone derivatives as nitric oxide inhibitory agent

Lam, Kok Wai; Uddin, Reaz; Liew, Choi Yi; Tham, Chau Ling; Israf, Daud Ahmad; Ahmad, Sadeem; Rahman, Mohd Basyaruddin Abdul; Ul-Haq, Zaheer; Lajis, Nordin Hj

doi:10.1007/s00044-011-9706-1

Cited by 14 publications

(7 citation statements)

References 28 publications

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“…The molecular properties described by the Lipinski's Rule of Five usually have a great effect on bioactivity. 36) These results suggested a partial influence of Lip_violation on the anti-inflammatory activity.…”

Section: Resultsmentioning

confidence: 93%

Relationship of Chemical Structure to in Vitro Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of Aphanamixis grandifolia

Guo

Wang

Zhang

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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A series of tirucallane triterpenoids isolated from the stem barks of Aphanamixis grandifolia were assessed for their anti-inflammatory activity, exhibiting from weak to strong anti-inflammatory activity, by testing their inhibitory effects on nitric oxide (NO) production and tumor necrosis factor-α (TNF-α) level in lipopolysaccharide (LPS) induced RAW264.7 murine macrophages. To explore the relationship between the structures and anti-inflammatory activity, a vast pool of molecular descriptors for each isolate were calculated. Genetic algorithms (GA) or simulated annealing (SA) based partial least squares (GA-PLS and SA-PLS) algorithms identified some important descriptor combinations, which were correlated with both sets of the anti-inflammatory data by partial least squares 2 (PLS2) method. S-Plot was used to visualize the descriptor influence in the PLS2 model, disclosed five most important molecular descriptors, nOHt, RDF150m, lip_vio-lation, Mor32m and JhetZ.Key words Aphanamixis grandifolia; tirucallane triterpenoid; anti-inflammatory activity; nitric oxide; tumor necrosis factor-α; structure-activity relationship Inflammation is a normal and crucial response of the organism to various stimuli including physical damage, ultra violet irradiation, microbial invasion and immune reactions, playing a pivotal role in host defense.1,2) While inflammatory cascades may cause pain, tissue damage, and a wide range of human acute and chronic inflammatory diseases, such as chronic asthma, rheumatoid arthritis and multiple sclerosis, and psoriasis.3) Many of these diseases with increasing incidence rate are particularly debilitating to the patient's functional capacity and quality of life.Macrophages have vital functions in maintaining body homeostasis, as well as in inflammatory processes, which are endowed with the ability to release a variety of mediators including the free radical nitric oxide (NO), 4) one of the most versatile regulator in the immune system. 5) Overproduction of NO can exacerbate inflammation, playing an important role in the pathogenesis of several chronic and systemic inflammation diseases, such as rheumatoid arthritis. 6,7)Tumor necrosis factor-α (TNF-α), one of the most important pro-inflammatory cytokines, is also massively produced by the activated macrophages and monocytes at local sites of inflammation.8) Its excessive production further triggers the secretion of other inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and thereby aggravates the inflammation in many autoimmune/inflammatory diseases. 9-11)Exposure to major anti-inflammatory agents, such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), is known to increase substantially the risk of serious side effects.3,12) Therefore, there is an unmet medical need for new treatment strategies, which could be possibly filled by rational phytopharmaceuticals with a favorable benefit/risk ratio. Recent investigations into the anti-inflamm...

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Section: Resultsmentioning

confidence: 93%

Relationship of Chemical Structure to in Vitro Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of Aphanamixis grandifolia

Guo

Wang

Zhang

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Syntheses of compounds 1a, 1b, 1c, 2a, 2b, 2c, 3a, 3b, 3c, 4a, 4b, 4c, 4e, 5b, 5c and 6e were reported previously (22,23), whereas compounds 4d, 5d, 6d, 6f, 6g, 7d, 7e, 7h, 7i, 8d and 8e were prepared in this study using the sodium hydroxide-catalysed Claisen-Schmidt condensation reaction.…”

Section: Methodsmentioning

confidence: 89%

Synthesis and Evaluation of Chalcone Derivatives as Inhibitors of Neutrophils' Chemotaxis, Phagocytosis and Production of Reactive Oxygen Species

et al. 2013

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Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti-inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol- and lucigenin-based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4-methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators.

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“…2-Hydroxychalcones 3 were synthesised by the condensation of salicylaldehyde with acetophenones according to known methods. 15,18,19 Synthesis of 1H-pyrazolo [3,4-b]pyridines 5; general procedure A mixture of the 2-hydroxychalcone derivatives (3, 0.5 mmol) and 3-methyl-1-phenyl-1H-pyrazol-5-amine (4, 0.5 mmol) and ZrCl 4 (29 mg, 0.125 mmol) was heated under reflux in anhydrous ethanol (5 mL). When the reactant disappeared (10 h, monitored by TLC), the mixture was cooled to room temperature and purified by column chromatography using petroleum ether-ethyl acetate as the eluent to deliver compounds 5.…”

Section: Methodsmentioning

confidence: 99%

ZrCl₄-Catalysed Synthesis of New 4-(2-hydroxyphenyl)Pyrazolo[3,4-b]Pyridine Derivatives

Liu

Yin

2015

Journal of Chemical Research

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Functionalised pyrazolo [3,4-b]pyridines have attracted everincreasing attention as they are widely present in numerous natural products, anxiolytic targets (such as cartazolate, etazolate and tracazolate) 1,2 and fluorescent dyes. 3 Therefore, a variety of methods have been reported for the preparation of pyrazolo [3,4-b]pyridine derivatives, most of them involving the multicomponent reactions of aldehydes, 5-aminopyrazoles and highly active methylene compounds catalysed by acetic acid, 4,5 L-proline 6,7 or microwave irradiation. 8 As a mild Lewis acid catalyst, zirconium(IV) chloride (ZrCl 4 ) has the advantage of low cost and low toxicity, but it has been rarely utilised in catalytic organic synthesis. [9][10][11] Recently, we have developed an efficient method for the synthesis of coumarin-and cyclohexandione-fused 2,8-oxazabicyclo[3.3.1] nonanes by the three-component reaction of 2-hydroxychalcones, 4-hydroxycoumarin/1,3-cyclohexandiones and aqueous ammonia. [12][13][14] On the basis of the possible intermolecular Michael addition/amination/intramolecular bicyclisation domino reaction mechanism and excellent nucleophilicity of 5-aminopyrazoles, we expected to be able to synthesise the pyrazole-fused 2,8-oxazabicyclo[3.3.1]nonane 6a from 2-hydroxychalcone 3a and 3-methyl-1-phenyl-1H-pyrazol-5-amine 4. However, it was found that the expected product did not form, and the reaction gave 4-(2-hydroxyphenyl)pyrazolo [3,4-b]pyridine 5a in excellent yield in the presence of ZrCl 4 (Table 1).

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Synthesis and QSAR analysis of chalcone derivatives as nitric oxide inhibitory agent

Cited by 14 publications

References 28 publications

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Synthesis and Evaluation of Chalcone Derivatives as Inhibitors of Neutrophils' Chemotaxis, Phagocytosis and Production of Reactive Oxygen Species

ZrCl₄-Catalysed Synthesis of New 4-(2-hydroxyphenyl)Pyrazolo[3,4-b]Pyridine Derivatives

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Synthesis and QSAR analysis of chalcone derivatives as nitric oxide inhibitory agent

Cited by 14 publications

References 28 publications

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Relationship of Chemical Structure to <i>in Vitro</i> Anti-inflammatory Activity of Tirucallane Triterpenoids from the Stem Barks of <i>Aphanamixis grandifolia</i>

Synthesis and Evaluation of Chalcone Derivatives as Inhibitors of Neutrophils' Chemotaxis, Phagocytosis and Production of Reactive Oxygen Species

ZrCl4-Catalysed Synthesis of New 4-(2-hydroxyphenyl)Pyrazolo[3,4-b]Pyridine Derivatives

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ZrCl₄-Catalysed Synthesis of New 4-(2-hydroxyphenyl)Pyrazolo[3,4-b]Pyridine Derivatives