Synthesis and innate immunosuppressive effect of 1,2-cyclopentanediol derivatives

Kikuchi, Haruhisa; Okazaki, Kaori; Sekiya, Motohiro; Uryu, Yasuyuki; Ueda, Kazunori; Katou, Yasuhiro; Kurata, Shoichiro; Oshima, Yoshiteru

doi:10.1016/j.ejmech.2011.01.049

Cited by 11 publications

(5 citation statements)

References 18 publications

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“…1 H NMR (400 MHz, CDCl 3 ) δ 4.66–4.65 (m, 2H), 3.70 (d, J = 6.8 Hz, 2H), 2.29–2.20 (m, 1H), 1.93–1.79 (m, 4H), 1.70 (brs, 1H), 1.49 (s, 3H), 1.30 (s, 3H). The spectroscopic data coincide with the previous report …”

Section: Methodssupporting

confidence: 92%

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Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors

Niu

Xiong

et al. 2015

J. Med. Chem.

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Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs. On the basis of the transition state of the enzyme-catalyzed sialylation reaction, we proposed that the cyclopentane skeleton in its two puckered conformations might mimic the planar structure of the donor (CMP-Neu5Ac) in the transition state. A series of cyclopentane-containing compounds were designed and synthesized by coupling different cyclopentane α-hydroxyphosphonates with cytidine phosphoramidite. Their inhibitory activities against recombinant human ST6Gal-I were assayed, and a potent inhibitor 48l with a Ki of 0.028 ± 0.006 μM was identified. The results show that the cyclopentanoid-type compounds could become a new type of sialyltransferase inhibitors as biological probes or drug leads.

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Section: Methodssupporting

confidence: 92%

“…1 The spectroscopic data coincide with the previous report. 82 Dibenzyl α-Hydroxy-(c-3,c-4-isopropylidenedioxy-r-1-cyclopentylmethyl)-phosphonate (20). To a solution of 19 (88.6 mg, 0.51 mmol) in CH 2 Cl 2 (2 mL) were added TEMPO (8.0 mg, 0.05 mmol) and BAIB (199.7 mg, 0.62 mmol) at 0 °C under argon atmosphere.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors

Niu

Xiong

et al. 2015

J. Med. Chem.

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“…To screen for compounds that target innate immunity, we established an ex vivo culture system based on the Drosophila IMD (IMmunoDeficiency) signaling pathway. , Drosophila is a model organism for genetic and molecular studies of innate immunity because of the striking conservation between the mechanisms that regulate insect immunity and mammalian innate immunity. , Specifically, the TNF-α signaling pathway in humans plays a critical role in the inflammatory response by producing co-stimulatory molecules, cytokines, chemokines, and adhesion molecules through the activation of NF-kB, which shares some similarity with the IMD pathway in Drosophila innate immunity. This system has been used to search for natural substances that regulate innate immunity of both humans and Drosophila . − In this paper, we describe the isolation and the elucidation of the structure of a cyclic depsipeptide, aspergillicin F ( 6 ) (Figure ), from the fungus Aspergillus sp. and the synthesis of aspergillicin A–F ( 1 – 6 ), which show innate immunity-modulating activity.…”

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confidence: 99%

Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of Aspergillicins with Innate Immune-Modulating Activity

et al. 2015

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Innate immunity is the front line of self-defense against microbial infection. After searching for natural compounds that regulate innate immunity using an ex vivo Drosophila culture system, we identified a new cyclic depsipeptide, aspergillicin F, from the fungus Aspergillus sp., as an innate immune suppressor. The total synthesis and biological evaluation of the aspergillicin family, including aspergillicin F, were performed, revealing that slight structural differences in the side chains of amino acid residues alter innate immunity-regulating activity.

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“…So far, compound 2 has not been reported as natural or synthetic product. Kikuchi et al [32] . have reported synthesis of compound 1 and several derivatives along with their immunosuppressive activity on Drosophila innate immunity.…”

Section: Resultsmentioning

confidence: 99%

Chemical Investigation of Marine‐Derived Fungus Aspergillus flavipes for Potential Anti‐Inflammatory Agents

Tilvi

Parvatkar

Singh

et al. 2021

Chemistry & Biodiversity

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The marine fungus, Aspergillus flavipes (MTCC 5220), was isolated from the pneumatophore of a mangrove plant Acanthus ilicifolius found in Goa, India. The crude extract of A. flavipes was found to show anti‐inflammatory activity. It blocked interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) production in lipopolysaccharide (LPS)‐activated THP‐1 cells with IC50 of 2.69±0.5 μM and 6.64±0.4 μM, respectively. The chemical investigation led to the isolation of optically inactive 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2β‐diol (1) along with a new optically active diastereoisomeric compound, 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2α‐diol (2). In addition, the fungus also produced known compounds (+)‐terrein (3), butyrolactone I (4) and butyrolactone II (5) in high yields. Among these, (+)‐terrein (3) exhibited IL‐6 and TNF‐α inhibition activity with IC50 of 8.5±0.68 μM and 15.76±0.18 μM, respectively, while butyrolactone I (4) exhibited IC50 of 12.03±0.85 μM (IL‐6) and 43.29±0.76 μM (TNF‐α) inhibition activity with low toxicity to host cells in LPS stimulated THP‐1 cells. This is the first report of the isolation and characterization of 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2α‐diol (2). The structures of all the isolated compounds were elucidated on the basis of extensive detailed NMR spectroscopic data. Anti‐inflammatory activity of the fungi A. flavipes is presented here for the first time, which was due to (+)‐terrein and butyrolactone I, as the major constituents and they can be further explored in the therapeutic area.

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Synthesis and innate immunosuppressive effect of 1,2-cyclopentanediol derivatives

Cited by 11 publications

References 18 publications

Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors

Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors

Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of Aspergillicins with Innate Immune-Modulating Activity

Chemical Investigation of Marine‐Derived Fungus Aspergillus flavipes for Potential Anti‐Inflammatory Agents

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