2-Styrylchromone derivatives as potent and selective monoamine oxidase B inhibitors

Takao, Koichi; Endo, Satoshi; Nagai, Junko; Kamauchi, Hitoshi; Takemura, Yuri; Uesawa, Yoshihiro; Sugita, Yoshiaki

doi:10.1016/j.bioorg.2019.103285

Cited by 26 publications

(18 citation statements)

References 27 publications

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“…Here, 2-styrylchromones ( B ) were synthesized by base-catalyzed condensation of the corresponding 2-methylchromones with selected benzaldehyde derivatives [ 24 ].…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

“…Compounds 38 , 39 , 87 , 89 , 153 , 173 , 177, and 236 inhibited monoamine oxidase (MAO-B) more effectively than pargyline, an irreversible selective MAO-B inhibitor drug. This suggests their application to treat the Parkinson’s disease and Alzheimer’s disease [ 24 , 27 , 28 , 30 , 55 ]. Halogen-containing compounds show more potent inhibitory activity.…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

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Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

et al. 2020

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Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, and 3 amides) gave a wide range of the intensity of tumor specificity, possibly reflecting the fitness for the optimal 3D structure and electric state. Among them, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound 22), which belongs to 3-styrylchromones, showed the highest tumor specificity. 22 induced subG1 and G2 + M cell population in human oral squamous cell carcinoma cell line, with much less keratinocyte toxicity as compared with doxorubicin and 5-FU. However, 12 active compounds selected did not necessarily induce apoptosis and mitotic arrest. This compound can be used as a lead compound to manufacture more active compound.

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“…Here, 2-styrylchromones ( B ) were synthesized by base-catalyzed condensation of the corresponding 2-methylchromones with selected benzaldehyde derivatives [ 24 ].…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

et al. 2020

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“…Synthesis of test compounds. 2-[(1E)-2-Phenylethenyl]-4H-1benzopyran-4-one [1], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-4H-1benzopyran-4-one [2], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-4H-1benzopyran-4-one [3], 2-[(1E)-2-(4-bromophenyl)ethenyl]-4H-1benzopyran-4-one [4], 2-[(1E)-2-(4-methoxyphenyl)ethenyl]-4H-1benzopyran-4-one [5], 2-[(1E)-2-(3,4-dimethoxy)ethenyl]-4H-1benzopyran-4-one [6], 6-methoxy-2-[(1E)-2-phenylethenyl]-4H-1benzopyran-4-one [7], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [8], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-6methoxy-4H-1-benzopyran-4-one [9], 2-[(1E)-2-(4-bromophenyl) ethenyl]-6-methoxy-4H-1-benzopyran-4-one [10], 6-methoxy-2-[(1E)-2-(4-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one [11], 2-[(1E)-2-(3,4-dimethoxy)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [12], 7methoxy-2-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one [13], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [14], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [15], 2-[(1E)-2-(4-bromophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [16], 7-methoxy-2-[(1E)-2-(4-methoxyphenyl) ethenyl]-4H-1-benzopyran-4-one [17], and 2-[(1E)-2-(3,4-dimethoxy) ethenyl]-7-methoxy-4H-1-benzopyran-4-one [18] were synthesized by the condensation of the corresponding 2-methylchromones with selected benzaldehyde derivatives, according to previous methods (19). All compounds were dissolved in DMSO at 40 mM and stored at -20˚C before use.…”

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confidence: 99%

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

et al. 2019

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Background/Aim: Studies of biological activity of 2styrylchromone derivatives focusing on antioxidant, antiinflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure-activity relationship (QSAR) analysis. Materials and Methods: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC 50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cellcycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2styrylchromone derivatives. Results: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG 1 and G 2 /M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. Conclusion: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds. Our group recently found that low-molecular weight natural polyphenols, such as tannins and flavonoids showed very low anticancer activity (evaluated by tumor-specificity with human cultured malignant and none-malignant cells) (1). On the other hand, chemical modification of chromone, two ring backbone structure present in flavonoids, yielded derivatives with much higher tumor-specificity (2, 3). 2-Styrylchromone is a derivative having a styryl group bonded to the 2-position of the chromone skeleton. Synthetic 2styrylchromone derivatives have been reported to show radical scavenging (4, 5), anti-inflammatory (6), hepatoprotective (7), neuroprotective (8-10), anti-human immunodeficiency virus (11), anti-norovirus (12), anti-rhinovirus (13, 14), antitumor (15-18), and monoamine oxidase B inhibiting (19) activity. However, very few studies tested their cytotoxicity against normal cells (16). In the present study, we investigated the cytotoxicity of eighteen synthetic 2-styrylchromone derivatives (Figure 1) against four human oral squamous cell carcinoma (OSCC) cells lines (Ca9-22, HSC-2, HSC-3, HSC-4) and three human normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligamental fibroblast (HPLF) and human pulp cell (HPC)], and performed quantitative structure-activity relationship (QSAR) analysis. Materials and Methods Materials.

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“…Piperic acid was prepared by alkaline hydrolysis of piperine [ 24 ]. Eighteen 2-styrylchoromone derivatives were synthesized by base-catalyzed condensation of the corresponding 2-methylchromones with selected benzaldehyde derivatives [ 25 ]. Fourteen 3-styrylchoromone derivatives were synthesized by Knoevenagel condensation of the corresponding 3-formylchromones with various phenylacetic acid derivatives [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we report the in vitro anti-HSV activity of 20 Kampo formulas and alkaline extracts of the leaves of Sasa sp. (SE) and pine cone combined with dextrin (PCE), representative polyphenols, and a total of 119 chromones, esters, and amides [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ], synthesized from chromone (to search for new type of anti-HSV agents), a back-bone structure of flavonoids, together with positive control acyclovir [ 27 ], representative polyphenols (resveratrol, p -coumaric acid, and curcumin used as negative controls) [ 19 ] and povidone iodine (PVP-I), a popular gargle [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Quantification of the Ability of Natural Products to Prevent Herpes Virus Infection

et al. 2020

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Background: Herpes simplex virus (HSV) is usually dormant and becomes apparent when body conditions decline. We investigated the anti-HSV activity of various natural and synthetic compounds for future clinical application. Methods: Mock- and HSV-infected Vero cells were treated for three days with various concentrations of samples. For short exposure, 100-fold concentrated virus were preincubated for 3 min with samples, diluted to normal multiplicity of infection (MOI), before the addition to the cells. Anti-HSV activity was evaluated by the chemotherapy index. Results: Alkaline extracts of the leaves of Sasa sp. (SE) and pine cone (PCE) showed higher anti-HSV activity than 20 Japanese traditional herb medicines (Kampo formulas), four popular polyphenols, and 119 chromone-related compounds. Exposure of HSV to SE or PCE for 3 min almost completely eliminated the infectivity of HSV, whereas much longer exposure time was required for Kakkonto, the most active Kampo formulae. Anti-HSV activity of PCE and Kakkonto could be detected only when they were dissolved by alkaline solution (pH 8.0), but not by neutral buffer (pH 7.4). Anti-HSV activity of SE and povidone iodine was stable if they were diluted with neutral buffer. Conclusions: The present study suggests the applicability of SE and PCE for treatment of oral HSV and possibly other viruses.

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2-Styrylchromone derivatives as potent and selective monoamine oxidase B inhibitors

Cited by 26 publications

References 27 publications

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

Quantification of the Ability of Natural Products to Prevent Herpes Virus Infection

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