PT  - JOURNAL ARTICLE
AU  - KOICHI TAKAO
AU  - KAORI HOSHI
AU  - HIROSHI SAKAGAMI
AU  - HAIXIA SHI
AU  - KENJIRO BANDOW
AU  - JUNKO NAGAI
AU  - YOSHIHIRO UESAWA
AU  - AKITO TOMOMURA
AU  - MINEKO TOMOMURA
AU  - YOSHIAKI SUGITA
TI  - Further Quantitative Structure–Cytotoxicity Relationship Analysis of 3-Styrylchromones
AID  - 10.21873/anticanres.13929
DP  - 2020 Jan 01
TA  - Anticancer Research
PG  - 87--95
VI  - 40
IP  - 1
4099  - http://ar.iiarjournals.org/content/40/1/87.short
4100  - http://ar.iiarjournals.org/content/40/1/87.full
SO  - Anticancer Res2020 Jan 01; 40
AB  - Background/Aim: Very few studies are available about the biological activity of 3-styrylchromones. Our previous study demonstrated the importance of methoxy group at 6-position of the chromone ring and hydroxyl group at 4’-position of phenyl group in styryl moiety. As a sequel of this study, we synthesized fourteen compounds that include eight 3-styrylchromones where methoxy group was introduced at 7-position of chromone rings, and then evaluated their tumor-specificity. Materials and Methods: Tumor-specificity (TS) was calculated by relative cytotoxicity against human oral squamous cell carcinoma cell lines versus human normal oral cells. Apoptosis induction and growth arrest were monitored by cell-cycle analysis. Quantitative structure–activity relationship analysis of TS was performed with 3,167 chemical descriptors. Results and Discussion: Two compounds, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one [7] and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [14] showed higher tumor-specificity than doxorubicin and 5-FU, suggesting the importance of methoxy group in 7-position of the chromone ring. These compounds induced the apoptosis and mitotic arrest in HSC-2 cells. The tumor-specificity of 3-styrylchromone derivatives were most correlated with descriptors for molecule shape and electronic charge. The present study suggested that modification by introducing methoxy group at 7-position, instead at 6-position, further increased the tumor-specificity of 3-styrylchromone.