Anti-nitric oxide production activity of isothiocyanates correlates with their polar surface area rather than their lipophilicity

Noshita, Toshiro; Kidachi, Yumi; Funayama, Hirokazu; Kiyota, Hiromasa; Yamaguchi, Hideaki; Ryoyama, Kazuo

doi:10.1016/j.ejmech.2009.08.005

Cited by 22 publications

(16 citation statements)

References 13 publications

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“…Then, we tried to apply Staudinger reaction and aza-Wittig reaction (Supporting Information Scheme S2). 17 To synthesize 2-azidoethyl methacrylate, a DMF solution of 2-bromoethyl methacrylate and sodium azide was stirred for 1 h at 60 C. After a usual workup, PPh 3 was added to the crude products, and the mixture was stirred for 12 h at room temperature. Adding of CS 2 to the mixture at room temperature gave ITEMA as colorless oil in 40% yield.…”

Section: Monomer Synthesismentioning

confidence: 99%

Stable heterocumulene monomer in water; Synthesis and polymerization of (meth)acrylates having an isothiocyanate structure

Seto

Matsumoto

Endō

2013

J. Polym. Sci. Part A: Polym. Chem.

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Novel methacrylate and acrylate monomers having an isothiocyanate structure, 2-isothiocyanatoethyl methacrylate (ITEMA) and 2-isothiocyanatoethyl acrylate (ITEA), were synthesized, and their radical polymerizations were examined, respectively. ITEMA and ITEA were synthesized by addition of carbon disulfide to 2-aminoethyl methacryrate or 2-aminoethyl acrylate, followed by treatment with ethyl chloroformate. Radical polymerizations of the obtained monomers (ITEMA, ITEA) were carried out methyl ethyl ketone using 2,2'-azobisisobutyronitrile (AIBN) as an initiator to obtain the corresponding polymers. The glass transition temperatures of the poly-ITEMA and poly-ITEA were determined to be 55 and 2 C by differential scanning calorimetry, respectively. The 5 wt % decomposition temperatures of the poly-ITEMA and poly-ITEA were determined to be 277 and 269 C by thermogravimetric analysis, respectively. Isothiocyanato groups in the monomers did not react with water in acetone solution at 60 C for 24 h to be tolerable to water.

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Section: Monomer Synthesismentioning

confidence: 99%

Stable heterocumulene monomer in water; Synthesis and polymerization of (meth)acrylates having an isothiocyanate structure

Seto

Matsumoto

Endō

2013

J. Polym. Sci. Part A: Polym. Chem.

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“…We recently found that 6- MITC, an ITC from a Japanese indigenous herb wasabi, demonstrated significant growth inhibitory activity toward a macrophage-like tumor cell line [6], suggesting that 6-MITC can be utilized for the antitumor drug development. However, the precise mode of 6-MITC binding is unknown.…”

Section: Resultsmentioning

confidence: 99%

“…We have been focusing our attention on ITCs as multifunctional agents for the prevention and treatment of cancer. Recently, we found that a naturally occurring ITC from wasabi ( Wasabia japonica ), a Japanese indigenous herb, and demonstrated significant growth inhibitory activity toward a macrophage-like tumor cell line [6]. These reports suggest that targeting P-gp with inhibitors from natural origin could be utilized for controlling the development and progression of cancer.…”

Section: Introductionmentioning

confidence: 99%

Homology modeling and structural analysis of human P-glycoprotein

Yamaguchi

Kidachi²,

Kamiie³

et al. 2012

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Homology modeling and structural analysis of human P-glycoprotein (hP-gp) were performed with a software package the Molecular Operating Environment (MOE). A mouse P-gp (mP-gp; PDB code: 3G5U) was selected as a template for the 3D structure modeling of hP-gp. The modeled hP-gp showed significant 3D similarities at the drug biding site (DBS) to the mP-gp structure. The contact energy profiles of the hP-gp model were in good agreement with those of the mP-gp structure. Ramachandran plots revealed that only 3.5% of the amino acid residues were in the disfavored region for hP-gp. Further, docking simulations between 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) and the P-gp models revealed the similarity of the ligand-receptor bound location between the hP-gp and mP-gp models. These results indicate that the hP-gp model was successfully modeled and analyzed. To the best of our knowledge, this is the first report of a hP-gp model with a naturally occurring isothiocyanate, and our data verify that the model can be utilized for application to target hP-gp for the development of antitumor drugs.AbbreviationsABC - ATP-binding cassette, ASE-Dock - alpha sphere and excluded volume-based ligand-protein docking, DBS - drug biding site, MDR - multidrug resistance, MOE - Molecular Operating Environment, ITC - isothiocyanate, P-gp - P-glycoprotein.

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“…Noshita et al [49] investigated the inhibitory activities of 6-MSITC and other synthesized ITCs against LPS-induced NO production using mouse peritoneal macrophages and mouse J774.1 macrophage-like cells. Among the tested ITCs, 6-MSITC indicated the strongest inhibition of NO production.…”

Section: Effect Of 6-msitc On Inflammatory Factorsmentioning

confidence: 99%

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

Uto

Hou

Morinaga

et al. 2012

Advances in Pharmacological Sciences

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6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages.

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Anti-nitric oxide production activity of isothiocyanates correlates with their polar surface area rather than their lipophilicity

Cited by 22 publications

References 13 publications

Stable heterocumulene monomer in water; Synthesis and polymerization of (meth)acrylates having an isothiocyanate structure

Stable heterocumulene monomer in water; Synthesis and polymerization of (meth)acrylates having an isothiocyanate structure

Homology modeling and structural analysis of human P-glycoprotein

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

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