Synthesis and evaluation of asymmetric curcuminoid analogs as potential anticancer agents that downregulate NF-κB activation and enhance the sensitivity of gastric cancer cell lines to irinotecan chemotherapy

Qiu, Peihong; Zhang, Shanshan; Zhou, Yangyang; Zhu, Min; Kang, Yanting; Chen, Dahui; Wang, Jiabing; Zhou, Peng; Li, Wulan; Xu, Qing; Jin, Rong; Wu, Jianzhang; Liang, Guang

doi:10.1016/j.ejmech.2017.08.022

Cited by 31 publications

(10 citation statements)

References 41 publications

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“…For example, the carotenoid lycopene, in addition to its antioxidant properties, inhibits transcriptional activity of NF-κB, down-regulates expression of IL-1β, IL-6, TNF, and COX2, and activates caspase-3 and caspase-9 in AGS cells [ 169 ]. Phyto-compound curcumin and its chemical analogs exert anti-GC effects by downregulating NF-κB activity [ 170 , 171 ]. Polyphenols capsaicin, quercetin, resveratrol, epigallocatechin-3-gallate, etc.…”

Section: Therapeutic Targeting Of Nf-κb In Gastric Cancermentioning

confidence: 99%

NF-κB in Gastric Cancer Development and Therapy

et al. 2021

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Gastric cancer is considered one of the most common causes of cancer-related death worldwide and, thus, a major health problem. A variety of environmental factors including physical and chemical noxae, as well as pathogen infections could contribute to the development of gastric cancer. The transcription factor nuclear factor kappa B (NF-κB) and its dysregulation has a major impact on gastric carcinogenesis due to the regulation of cytokines/chemokines, growth factors, anti-apoptotic factors, cell cycle regulators, and metalloproteinases. Changes in NF-κB signaling are directed by genetic alterations in the transcription factors themselves, but also in NF-κB signaling molecules. NF-κB actively participates in the crosstalk of the cells in the tumor micromilieu with divergent effects on the heterogeneous tumor cell and immune cell populations. Thus, the benefits/consequences of therapeutic targeting of NF-κB have to be carefully evaluated. In this review, we address recent knowledge about the mechanisms and consequences of NF-κB dysregulation in gastric cancer development and therapy.

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Section: Therapeutic Targeting Of Nf-κb In Gastric Cancermentioning

confidence: 99%

NF-κB in Gastric Cancer Development and Therapy

et al. 2021

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“…Most of the previously reported synthetic work focused on the development of new symmetric curcuminoids with a similar antioxidant profile as curcumin but with different aromatic substitution patterns [71][72][73]. However, only a few attempts have been developed recently to explore asymmetrical substitution patterns of curcumin [74][75][76].…”

Section: Introductionmentioning

confidence: 99%

1,5-Benzodiazepin-2(3H)-ones: In Vitro Evaluation as Antiparkinsonian Agents

et al. 2021

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A new series of twenty-three 1,5-benzodiazepin-2(3H)-ones were synthesized and evaluated in the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays as a new chemotype with antioxidant and good drug-like properties. All of the derivatives showed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y and the human hepatoma HepG2 cell lines. Experimental solubility in bio-relevant media showed a good relationship with melting points in this series. Five compounds with the best antioxidant properties showed neuroprotectant activity against H2O2-induced oxidative stress in the SH-SY5Y cell line. From them, derivatives 4-phenyl-1H-1,5-benzodiazepin-2(3H)-one (18) and 4-(3,4,5-trimethoxyphenyl)-1H-1,5-benzodiazepin-2(3H)-one (20) yielded good neuroprotection activity in the same neuronal cell line under 6-OHD and MPP+ insults as in vitro models of mitochondrial dysfunction and oxidative stress in Parkinson’s disease (PD). Both compounds also demonstrated a significant reduction of intracellular Reactive Oxygen Species (ROS) and superoxide levels, in parallel with a good improvement of the Mitochondrial Membrane Potential (ΔΨm). Compared with curcumin, compound 18 better reduced lipid peroxidation levels, malondialdehyde (MDA), in SH-SY5Y cells under oxidative stress pressure and recovered intracellular glutathione synthetase (GSH) levels. Apoptosis and caspase-3 levels of SH-SY5Y under H2O2 pressure were also reduced after treatment with 18. Neuroprotection in neuron-like differentiated SH-SY5Y cells was also achieved with 18. In summary, this family of 1,5-benzodiazepin-2-ones with an interesting antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitutes a new promising chemical class with high potential for the development of new therapeutic agents against PD.

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“…The Synthesis of Compound A-N, 1A-10A and 1H-10H were performed as previously published. [19][20][21][22]…”

Section: Chemical and Synthesizementioning

confidence: 99%

Design, synthesis, and evaluation of mono‐carbonyl analogues of curcumin (MCACs) as potential antioxidants against periodontitis

Zhao

Zheng

Zhang

et al. 2021

J of Periodontal Research

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Background and objective:The application of curcumin is limited by its instability.Mono-carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. Materials and methods:The cytotoxicity of MCACs on MC3 T3-E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H 2 O 2 -induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature-induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers.Results: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A-10A, 1H-10H), among which, 1A exhibited the most potent cytoprotective effect against H 2 O 2 -induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO-1. Micro-CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO-1, and decreased TNFα and IL-1β. Conclusion:The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis.

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Synthesis and evaluation of asymmetric curcuminoid analogs as potential anticancer agents that downregulate NF-κB activation and enhance the sensitivity of gastric cancer cell lines to irinotecan chemotherapy

Cited by 31 publications

References 41 publications

NF-κB in Gastric Cancer Development and Therapy

NF-κB in Gastric Cancer Development and Therapy

1,5-Benzodiazepin-2(3H)-ones: In Vitro Evaluation as Antiparkinsonian Agents

Design, synthesis, and evaluation of mono‐carbonyl analogues of curcumin (MCACs) as potential antioxidants against periodontitis

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