Synthesis and assessment of phenylacrylamide derivatives as potential anti-oxidant and anti-inflammatory agents

Gu, Xiaoke; Chen, Jing; Zhang, Yinpeng; Guan, Mingyu; Li, Xin; Zhou, Qingqing; Song, Qinghua; Qiu, Jingying

doi:10.1016/j.ejmech.2019.07.020

Cited by 17 publications

(9 citation statements)

References 33 publications

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“…These results suggest that protection of the cells against D-galactose-induced oxidative stress by the six flavonoids was related to the regulation of antioxidant enzymes, lipid peroxidation, and the expression of liver antioxidant genes. Oxidative stress is thought to play a key role in promoting the secretion of inflammatory cytokines and gene expression of proinflammatory cytokines [ 45 , 46 ]. IL-10 represses the proinflammatory response and serum IL-10 decreases significantly in the D-galactose-treated mice [ 7 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

et al. 2020

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The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.

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Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

et al. 2020

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“…To clarify the potential mechanism of 3h , we firstly determined whether compound 3h could affect the expression and/or function of P‐gp, and found that 3h could not affect the efflux function as well as the expression of P‐gp (data not shown). Considering that one of the mechanisms underlying CS is the elevated production of ROS in drug resistant cell that overexpresses ABC transporters, [19,20] we subsequently measured the effect of 3h on the ROS level in drug resistant K562/A02 cells as well as the parental sensitive K562 cells using DCFHA‐DA assay [21] …”

Section: Resultsmentioning

confidence: 99%

Assessment of Thiosemicarbazone‐Containing Compounds as Potential Antileukemia Agents against P‐gp Overexpressing Drug Resistant K562/A02 Cells

Guan

Jiang

et al. 2021

Chemistry & Biodiversity

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P‐Glycoprotein (P‐gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone‐containing compounds were prepared and evaluated as potential antileukemia agents against drug resistant K562/A02 cell overexpressing P‐gp. Among them, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could significantly inhibit K562/A02 cells proliferation with an IC50 value of 0.96 μM. Interestingly, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could dose‐dependently increase ROS levels of drug resistant K562/A02 cells, thus displaying a potential collateral sensitivity (CS)‐inducing effect and selectively killing K562/A02 cells. Furthermore, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide possessed potent inhibitory effect on HDAC1 and HDAC6, and could promote K562/A02 cells apoptosis via dose‐dependently increasing Bax expression, reducing Bcl‐2 protein level, and inducing the cleavage of PARP and caspase3. These present findings suggest that N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide might be a promising lead to discover novel antileukemia agents against P‐gp overexpressing leukemic cells.

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“…In vitro studies with a synthetic chalcone (6a) of the phenylacrylamide class disclosed that the compound contributed to decreased production of nitrite and pro-inflammatory cytokines in mesan- In vitro studies with a synthetic chalcone (6a) of the phenylacrylamide class disclosed that the compound contributed to decreased production of nitrite and pro-inflammatory cytokines in mesangial cells induced by LPS. The suppressor mechanism involved the activation of the factor Nrf2 (nuclear factor erythhroid 2 related factor 2), which seems to be one of the main ones involved in the expression of antioxidant proteins modulating inflammatory and immunological responses [30].…”

Section: Biological Activitymentioning

confidence: 99%

“…gial cells induced by LPS. The suppressor mechanism involved the activation of the factor Nrf2 (nuclear factor erythhroid 2 related factor 2), which seems to be one of the main ones involved in the expression of antioxidant proteins modulating inflammatory and immunological responses [30]. Nrf2-dependent antioxidant genes, such as heme-oxygenase-1 (OH-1) and NADP dehydrogenase quinone (NQO-1), among others, act by blocking TNF-α-in addition to several monocyte chemotactic proteins and macrophage inflammatory proteins-thereby suppressing several inflammatory mediators as a result of reduced exposure to oxidative stress in target cells; and thus reducing the overproduction of cytokines that would activate the NF-κB pathway [31].…”

Section: Biological Activitymentioning

confidence: 99%

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

Silva

Almeida

Silva

et al. 2020

IJMS

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The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.

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Synthesis and assessment of phenylacrylamide derivatives as potential anti-oxidant and anti-inflammatory agents

Cited by 17 publications

References 33 publications

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

Assessment of Thiosemicarbazone‐Containing Compounds as Potential Antileukemia Agents against P‐gp Overexpressing Drug Resistant K562/A02 Cells

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

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