Koichi Takao1, Kaori Hoshi1, Hiroshi Sakagami2, Haixia Shi3,4, Kenjiro Bandow5, Junko Nagai6, Yoshihiro Uesawa6, Akito Tomomura5, Mineko Tomomura7, Yoshiaki Sugita1. 1. Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan. 2. Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan sakagami@dent.meikai.ac.jp. 3. Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan. 4. Shanghai Ninth People's Hospital, Shanghai Jiatong University School of Medicine, Shanghai, P.R. China. 5. Division of Biochemistry, Meikai University School of Dentistry, Saitama, Japan. 6. Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo, Japan. 7. Department of Oral Health Sciences, Meikai University School of Sciences, Chiba, Japan.
Abstract
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. Copyright
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 humanoral 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. Copyright
Authors: Praveen K Roayapalley; Hiroshi Sakagami; Keitaro Satoh; Shigeru Amano; Kenjiro Bandow; Renato J Aguilera; Karla G Cano Hernandez; Austre Y Schiaffino Bustamante; Stephen G Dimmock; Rajendra K Sharma; Umashankar Das; Jonathan R Dimmock Journal: Medicines (Basel) Date: 2021-12-16