Potent HGF/c-Met Axis Inhibitors from Eucalyptus globulus: the Coupling of Phloroglucinol and Sesquiterpenoid Is Essential for the Activity

Yang, Sheng‐Ping; Zhang, Xiaowei; Ai, Jing; Gan, Li‐She; Xu, Jin‐Biao; Wang, Ying; Su, Zushang; Wang, Lu; Ding, Jian; Geng, Meiyu; Yue, Jian‐Min

doi:10.1021/jm3007454

Cited by 47 publications

(49 citation statements)

References 25 publications

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“…Phloroglucinols in E. globulus are reported to possess cytotoxic, [2] antiviral, [3] [4] granulation inhibition, [5] [6] HIV-RTase inhibition, [7] antibacterial, [8] as well as HGF/c-Met axis inhibition activities. [9] In this article, we describe the isolation and structure elucidation of one new phloroglucinol (1), as well as five known phloroglucinol derivatives (2 -6), obtained from the fruits of this plant. The cytotoxicities of these phloroglucinols were performed against human lung (A549), murine breast (4T1), and skin (B16F10) cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Pham

Mohammad

et al. 2018

Chemistry & Biodiversity

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A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 - 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D- and 2D-NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 - 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase-3 levels in A549 cells were also determined by Western-blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5-fold and increased 10-folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11-fold increase in the level of caspase-3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.

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Section: Introductionmentioning

confidence: 99%

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Pham

Mohammad

et al. 2018

Chemistry & Biodiversity

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“…Biosynthetically, they are proposed to be adducts of phloroglucinol derivatives and terpenoids via hetero-Diels-Alder or carbocation-induced stepwise reactions 6, 10 . So far more than 100 phloroglucinol-coupled terpenoids have been reported 11, 18 , and their intriguing structures and important biological activities have attracted broad interest from both natural products and synthetic chemists over the last half century 5, 19–24 . For instance, psiguadials A, C, and D 9, 10 , hyperjapones A–E 16 , and hyperjaponols A and C 17 with novel skeletons and appealing pharmacological activities (e.g., antitumor and antiviral properties) have been synthesized by several groups 25, 26 .…”

Section: Introductionmentioning

confidence: 99%

Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava

Dong

Guo

Cheng

et al. 2017

Sci Rep

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Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A–K (1–11), along with 17 known ones (12–28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring. Putative biosynthetic pathways towards 1 and 2 are proposed. Compounds 1–13 and 16–26 exhibited moderate inhibitory activities against phosphodiesterase-4 (PDE4), a drug target for asthma and chronic obstructive pulmonary disease, with IC50 values in the range of 1.34–7.26 μM.

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“…Formyl-phloroglucinol meroterpenoids (FPMs) such as macrocarpals [1] and euglobals [2] are typical secondary metabolites of the genera Eucalyptus [3] and Psidium. [4] Aw ide range of bioactivities has been reportedf or these natural products, including antitumor, [5] antimicrobial, [3a, 6] and anti-HIV effects. [7] These phloroglucinol-terpeneh ybridsa re characterized by the connectiono fadiformylated phloroglucinol to varioust erpene moieties.…”

Section: Introductionmentioning

confidence: 99%

¹H NMR‐Guided Isolation of Formyl‐Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta

Shang

Yang

Jian

et al. 2016

Chemistry A European J

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Nine formyl-phloroglucinolmeroterpenoids (FPMs), namely, eucalrobusones A-I (1-9), were isolated from the leaves of Eucalyptus robusta by tracking the phenolic hydroxyl (1) H NMR peaks. The Snatzke helicity rules for the Cotton effects of twisted benzene rings were applied to elucidate the absolute configurations of the FPMs. These findings, along with NMR spectroscopy, the circular dichroism (CD) exciton chirality method, and CD calculations, allowed complete structures for the FPMs to be assigned. Eucalrobusones A-F (1-6) are novel adducts formed between a formyl-derived carbon atom on the phloroglucinol ring and monoterpene and sesquiterpene components. Eucalrobusones G-I (7-9) are the first examples of FPMs with cubebane part structures connected by an unusual 1-oxaspiro[5.5]undecane subunit. Among these isolates, eucalrobusone C (3) showed significant cytotoxicity against HepG2, MCF-7, and U2OS cancer cell lines, with IC50 values less than 10 μm. Compound 3 significantly blocks cell proliferation in MCF-7 cells and induces MCF-7 cell death through apoptosis.

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Potent HGF/c-Met Axis Inhibitors from Eucalyptus globulus: the Coupling of Phloroglucinol and Sesquiterpenoid Is Essential for the Activity

Cited by 47 publications

References 25 publications

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava

¹H NMR‐Guided Isolation of Formyl‐Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta

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Potent HGF/c-Met Axis Inhibitors from Eucalyptus globulus: the Coupling of Phloroglucinol and Sesquiterpenoid Is Essential for the Activity

Cited by 47 publications

References 25 publications

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava

1H NMR‐Guided Isolation of Formyl‐Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta

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¹H NMR‐Guided Isolation of Formyl‐Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta