Recent Progress of Basic Studies of Natural Products and Their Dental Application

Abstract

The present article reviews the research progress of three major polyphenols (tannins, flavonoids and lignin carbohydrate complexes), chromone (backbone structure of flavonoids) and herbal extracts. Chemical modified chromone derivatives showed highly specific toxicity against human oral squamous cell carcinoma cell lines, with much lower toxicity against human oral keratinocytes, as compared with various anticancer drugs. QSAR analysis suggests the possible correlation between their tumor-specificity and three-dimensional molecular shape. Condensed tannins in the tea extracts inactivated the glucosyltransferase enzymes, involved in the biofilm formation. Lignin-carbohydrate complexes (prepared by alkaline extraction and acid-precipitation) and crude alkaline extract of the leaves of Sasa species (SE, available as an over-the-counter drug) showed much higher anti-HIV activity, than tannins, flavonoids and Japanese traditional medicine (Kampo). Long-term treatment with SE and several Kampo medicines showed an anti-inflammatory and anti-oxidant effects in small size of clinical trials. Although the anti-periodontitis activity of synthetic angiotensin II blockers has been suggested in many papers, natural angiotensin II blockers has not yet been tested for their possible anti-periodontitis activity. There should be still many unknown substances that are useful for treating the oral diseases in the natural kingdom.

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

“…Computational analysis. QSAR analysis of cytotoxicity and tumor-specificity of eighteen 2-styrylchromone derivatives [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] were next performed. Since significant correlation (p<0.05) was found between cytotoxicity against tumor and normal cells, and TS with 139, 472 and 67 chemical descriptors (data not shown), top six chemical descriptors were chosen for QSAR analysis (Figures 4, 5 and 6; Table II).…”

“…The difference (T-N) was used as a tumor-specificity index in the following analyses (21). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] investigated in this study. Hungary) (23), was optimized by CORINA Classic (Molecular Networks GmbH, Germany) with forcefield calculations (amber-10: EHT) in Molecular Operating Environment (MOE) version 2018.0101 (Chemical Computing Group Inc., Quebec, Canada) (24).…”

“…We previously reported that [5] (identical with the compound 3 in (18)) induced internucleosomal DNA fragmentation and Figure 4. Top six chemical descriptors that showed higher correlation with cytotoxicity of eighteen 2-styrylchromone derivatives [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] against OSCC cells. The mean negative log CC 50 values (T) against tumor cells were plotted.…”

“…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.…”

In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs

“…We have recently reported that classical anticancer drugs exerted both good effect [extremely higher cytotoxicity against human oral squamous cell carcinoma (OSCC) cell lines than human normal oral mesenchymal cells], and bad effect (potent cytotoxicity against human normal oral epithelial cells) (2,3). Recently, moleculartargeted drugs, such as cetuximab (Cmab) and nivolumab (Nmab) have been approved for the treatment of head and neck cancer in Japan (November 10, 2016).…”