A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation

Chen, Qiao‐Hong; Yu, Kevin Shengyang; Zhang, Xiaojie; Chen, Guanglin; Hoover, A.; León, Francisco; Wang, Rubing; Subrahmanyam, Nithya; Mekuria, Ermias Addo; Rakotondraibe, L. Harinantenaina

doi:10.1016/j.bmcl.2015.08.064

Cited by 27 publications

(27 citation statements)

References 29 publications

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“…The present study used 1-chromonyl-5-imidazolylpentadienone, KY-20-22, which contains the pharmacophore of both curcumin and quercetin. The previous study suggested that this dienone induced an anti-proliferative effect in prostate cancer cells [30]. Further study found that this dienone is more potent and exhibit higher bioavailability compared to curcumin [31].…”

Section: Anti-proliferative Action Of 1-chromonyl-5-imidazolylpentadimentioning

confidence: 84%

“…This compound possesses a nitrogen-containing heteroaromatic ring, a molecular weight of 320, a Clog P of 1.89, and a tPSA of 59, implying a high probability of its good oral bioavailability. Earlier studies demonstrated that this compound exhibits anti-proliferative action in prostate cancer cells [30]. The five-membered heterocyclic ring in the dienone has been established as the optimal bioisostere of the phenyl ring in curcumin by making significant contributions to the improved potency in prostate cancer cells and superior bioavailability in rats [31].…”

Section: Introductionmentioning

confidence: 99%

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1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel

Modi

Lawson

Chen

et al. 2020

IJMS

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Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial–mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.

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Section: Anti-proliferative Action Of 1-chromonyl-5-imidazolylpentadimentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel

Modi

Lawson

Chen

et al. 2020

IJMS

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“…Over the past few years, the synthesis and study of pharmacological activity of 1,4-pentadien-3-one derivatives attracted the attention of many chemists (Wang et al, 2017;Zhou et al, 2017). Further study on the structural optimization of 1,4-pentadien-3-one found that introducing benzotriazin-4(3H)-one (Zhang et al, 2018), imidazole (Samaan et al, 2014), thiazole (Wang et al, 2015), or chromone (Chen et al, 2015) moieties (Figure 1. A-D), could greatly enhance biological activities.…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds (v0.1)"

2020

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Background: Literatures revealed that 1,4-pentadien-3-one and triazine derivatives exhibited a wide variety of biological activities. In order to develop highly bioactive molecules, in this study, a series of novel 1,4-pentadien-3-one derivatives containing triazine moieties were synthesized and their antibacterial and antiviral activities were investigated. Methods : A series of novel 1,4-pentadien-3-one derivatives containing triazine moieties were synthesized and characterized in detail via 1 H NMR, 13 C NMR and HRMS spectra. The antibacterial activities against Xanthomonas axonopodispv. citri (Xac), Xanthomonas oryzaepv. oryzae (Xoo) and Ralstonia solanacearum (R.s) were evaluated at 100 and 50 µg/mL using a turbidimeter and N. tabacun L. leaves under the same age as that of test subjects. The curative, protective and inactivation activities against tobacco mosaic virus (TMV) at a concentration of 500 μg/mL were evaluated via the half-leaf blight spot method. Results: The bioassay results showed that some of the target compounds exhibited fine antibacterial activities against Xac and R.s. Particularly, half maximal effective concentration (EC 50) values of some target compounds against R.s are visibly better than that of the positive control bismerthiazol (BT). Notably, compound 4a showed excellent inactivation activity against TMV with a EC 50 value of 12.5 μg/mL, which was superior to that of ningnanmycin (NNM,13.5 μg/mL). Besides, molecular docking studies for 4a with tobacco mosaic virus coat protein (TMV-CP) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. These findings indicate that 1,4-pentadien-3-one derivatives containing triazine moieties may be potential antiviral and antibacterial agents.

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“…Although genistein possesses various biological activities, its poor solubility and low bioavailability limited its potential in clinical treatment , . Therefore, a large number of studies have been done to improve its pharmaceutical activities by structural modification of genistein . Zheng designed and synthesized a series of genistein derivatives by alkylation of C5, C7 and C4’‐ hydroxy group, and the analogue with 4’, 5‐dioctoxy‐7‐difluoromethane showed the best cytotoxic activity against HL‐60, HT‐29, and SGC‐7901 cells.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Genistein Amino Acid Ester Derivatives as Potential Anti‐Tumor Agents

et al. 2019

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Thirty‐one novel genistein amino acid ester derivatives were synthesized and evaluated for their anti‐proliferative activities against HUVEC cells and five cancer cells lines (HCT‐116, HeLa, HepG‐2, MCF‐7, MGC‐803). Most of the amino acid ester derivatives exhibited more inhibitory activity than their parent compound genistein. In particular, compound 8 j (methyl(4‐((5‐hydroxy‐3‐(4‐hydroxyphenyl)‐4‐oxo‐4H‐chromen‐7‐yl)oxy)butanoyl)tryptophanate) bearing tryptophan chain showed the most cytotoxicity against HCT‐116 cells with IC50 value of 2.76 μM. Further mechanistic studies indicated that compound 8 j suppressed HCT‐116 cell metastasis and induced cell apoptosis in a dose‐dependent manner. Cell cycle assay showed that compound 8 j arrested the HCT‐116 cells to G1 phase. These studies suggested compound 8 j might be a potential candidate for developing new anticancer drugs.

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A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation

Cited by 27 publications

References 29 publications

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel

Peer Review #1 of "Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds (v0.1)"

Synthesis and Biological Evaluation of Novel Genistein Amino Acid Ester Derivatives as Potential Anti‐Tumor Agents

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