Synthesis and Biological Evaluation of 7-O-Modified Formononetin Derivatives

Yang, Ying; Mao, Wenjun; Li, Huan‐Qiu; Zhu, Tao-Tao; Shi, Lei; Lv, Peng‐Cheng; Zhu, Hai‐Liang

doi:10.1155/2008/209830

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…These estrogenic metabolites also possess anticancer properties, such as inducing cell apoptosis (Jin et al, 2010; Zongliang et al, 2016). In this regard, several studies also designed and synthesized a series of novel formononetin derivatives or analogues exerting interesting anticancer properties (Yang et al, 2008; Ren et al, 2012; Fu et al, 2017; Lin et al, 2017).…”

Section: Overview Of Formononetinmentioning

confidence: 99%

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

et al. 2019

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Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C 16 H 12 O 4 ), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus . The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.

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Section: Overview Of Formononetinmentioning

confidence: 99%

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

et al. 2019

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“…Yang et al reported the antimicrobial effects of FMN against Gram-positive and Gram-negative bacteria, e.g., Enterobacter cloacae, Escherichia coli, and Pseudomonas aeruginosa (22). Wang et al revealed the antiviral effects of FMN on enterovirus-51, whereas this fraction reduced enterovirus-51 RNA and protein synthesis (23).…”

Section: Discussionmentioning

confidence: 99%

Antiparasitic Effects and Cellular Mechanisms of Formononetin (a Natural Isoflavone) Against Hydatid Cyst Protoscoleces

Haghighi

Khalaf

Mahmoudvand

et al. 2023

Jundishapur J Nat Pharm Prod

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Background: The chemical agents applied to reduce the complications of hydatid cyst surgery are not free of side effects. Formononetin (FMN), as a natural isoflavone, has been shown to have various therapeutic benefits. Objectives: We studied the in vitro and ex vivo protoscolicidal activity and cellular mechanisms of FMN against hydatid cyst protoscoleces. Methods: Formononetin at 75, 150, and 300 μg/mL was mixed with hydatid cyst protoscoleces (103/mL), and the viability was determined in 5 to 60 min through eosin staining assay. The effect of FMN on caspase-3 activity was tested through a commercial colorimetric protease kit. In addition, the penetrability of the plasma membrane of protoscoleces after exposure to FMN was also determined by the SYTOX assay. Results: Formononetin at 300 μg/mL completely destroyed hydatid cyst protoscoleces after 30 minutes. While at 150 μg/mL, after 60 minutes of contact, 100% of protoscoleces were eliminated. By ex vivo assay, FMN showed its antiparasitic effect for longer periods. Based on these results, FMN at 300 μg/mL concentration completely eliminated hydatid cyst protoscoleces after 60 minutes of exposure. While at a concentration of 150 μg/mL after 60 minutes, 89.6% of protoscoleces were destroyed. Formononetin noticeably increased (P < 0.001) the activity of caspase-3 and the permeability of protoscoleces dose-dependently. Conclusions: Formononetin as a natural product showed promising effects on the protoscoleces of hydatid cysts, indicating that it can be considered a valuable scolicidal agent. However, additional investigations are necessary to evaluate its efficacy in animal models and human subjects.

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“…In recent years, the antileishmanial effects of a number of flavones-rich compounds, e.g., luteolin, 7,8-dihydroxyflavone, rhamnetin, 3-hydroxyflavone, catechol, 7,8,3′,4′-tetrahydroxyflavone, and apigenin against L. amazonensis L. donovani, and L. tropica have been reported (21,22). A review reported the potent antimicrobial effects of 7HMI against Staphylococcus aureus, S. aureus, S. epidermidis, Pseudomonas aeruginosa, Candida albicans, C. tropicalis, Cryptococcus neoformans, and enterovirus-51 viruses (23)(24)(25). A previous stud also reported that 7HMI significantly repressed the attachment, flagellar motility, and viability of Giardia trophozoites in mice (26).…”

Section: Discussionmentioning

confidence: 99%

Antiparasitic and cytotoxicity effects of 7-hydroxy-4′- methoxy isoflavone against Leishmania major

Aghaei,

Alizadegan,

Raziani

et al. 2023

J Herbmed Pharmacol

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Introduction: Leishmaniasis caused by Leishmania spp. is observed in most parts of the world. Although, glucantime, a pentavalent antimony compound, and other synthetic drugs are broadly applied for leishmaniasis therapy; however, the use of these synthetic agents has some limitations. Hence, this study was designed to assess the inhibiting effects of 7-hydroxy4′-methoxyisoflavone (7HMI) against promastigote and amastigote stages of Leishmania major in vitro. Methods: The MTT assay was applied to study the antileishmanial activity of 7HMI against promastigotes and its cytotoxicity effects on macrophage cells. The nitric oxide (NO) produced by the treated macrophage cells with 7HMI was also assessed. Results: 7HMI considerably (P<0.05) inhibited the growth rate of promastigotes and amastigotes stages. The 50% inhibitory concentrations of 7HMI and glucantim were 11.3 and 15.4 µg/mL for promastigote and amastigote, respectively. 7HMI, especially at 1/3 IC50 and 1/2 IC50 concentrations, considerably triggered the NO release. Conclusion: The current research findings reported the favorable antileishmanial effects of 7HMI against L. major with possible mechanisms such as reducing the infectivity rate of macrophage cells and provoking NO creation. Nevertheless, more research must be performed to clear its efficacy in animal model and then in human.

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Synthesis and Biological Evaluation of 7-O-Modified Formononetin Derivatives

Cited by 11 publications

References 16 publications

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

Antiparasitic Effects and Cellular Mechanisms of Formononetin (a Natural Isoflavone) Against Hydatid Cyst Protoscoleces

Antiparasitic and cytotoxicity effects of 7-hydroxy-4′- methoxy isoflavone against Leishmania major

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