Quantitative Structure–Cytotoxicity Relationship of 3-(<i>N</i>-Cyclicamino)chromone Derivatives

Shi, Huidong; Nagai, Junko; Sakatsume, Tsukasa; Bandow, Kenjiro; Okudaira, Noriyuki; Uesawa, Yoshihiro; Sakagami, Hiroshi; Tomomura, Mineko; Tomomura, Akito; Takao, Koichi; Sugita, Yoshiaki

doi:10.21873/anticanres.12748

Cited by 10 publications

(9 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We investigated a total 291 compounds from 17 different groups ( A~Q ) of their cytotoxicity (assessed by CC 50 ) against four human OSCC (Ca9-22, HSC-2, HSC-3, and HSC-4) and three human normal mesenchymal cells (HGF, HPLF, and HPC), and then their tumor specificity (assessed by TS M , calculated as describe in Figure 2 , and potency-selectivity expression (PSE)) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. PSE, that reflects both tumor specificity and cytotoxicity against tumor cells, was calculated by dividing the TS M by CC 50 for tumor cells, and then multiplying by 100.…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

“…This demonstrated that only limited numbers of compounds show higher tumor specificity, although their structures are very similar with each other. It is possible that such highly tumor-specific compounds show the optimal 3D structure, since the tumor specificity of chromone compounds shows the tight correlation with chemical descriptors that reflect the 3-D structure ( Table 4 ) [ 33 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Development Of Newly Synthesized Chromone Derivatives Witmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the treatment of cancer patients, both tumor-specificity (TS) and cytotoxicity (reciprocal of CC 50 value) of anticancer drugs should be considered. PSE, that is the product of these two factors was calculated using the following equation: PSE=100×TS/CC 50 (tumor cells) [that is, 100×D/B 2 (HGF+HPLF+HPC vs. Ca9-22 + HSC-2+HSC-3+HSC-4) and 100×C/A 2 (HGF vs. Ca9-22 in Table I) (10).…”

Section: Calculation Of Potency-selectivity Expression (Pse)mentioning

confidence: 99%

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background/Aim: The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs. Materials and Methods: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index. Results: Most of the classical anticancer drugs showed much higher antitumor activity than moleculartargeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a moleculartargeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG 1 population, but induced G 2 /M or G 1 /S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity. Conclusion: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.

show abstract

“…Chromone (4 H -1-benzopyran-4-one) is a backbone structure of flavonols, flavones, flavanones and isoflavones [29] (Figure 1B). We synthesized eight classes of chromones derivatives (total 134 compounds): 3-styrylchromones (15 compounds) [30,31] (containing compound A), 3-benzylidenechromanones (17 compounds) [32] (containing compound B), 3-styryl-2 H -chromenes (16 compounds) [33] (containing compound C), 2-azolylchromones (24 compounds) [34] (containing compound D), 3-( N -cyclicamino)chromones (15 compounds) [35] (containing compound E), 2-( N -cyclicamino)chromones (15 compounds) [36] (containing compound F), furo[2,3- b ]chromones (12 compounds) [37] (containing compound G) and pyrano[4,3- b ]chromones (20 compounds) [38] (containing compound H). The eight compounds that produced the highest TS value in each group are listed in Figure 4.…”

Section: Chromone Derivatives As New Type Of Anticancer Candidatementioning

confidence: 99%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Quantitative Structure–Cytotoxicity Relationship of 3-(N-Cyclicamino)chromone Derivatives

Cited by 10 publications

References 7 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

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

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

Contact Info

Product

Resources

About