Abstract
In order to explore the detailed structure-activity relationship (SAR) around xanthone scaffold bearing hydroxyl and prenyl moieties, twenty-nine natural and non-natural hydroxylated and prenylated xanthones have been synthesized and evaluated for their in vitro anti-proliferative activities against five human cancer cell lines, including HepG2 (hepatocelluar carcinoma), HCT-116 (colon carcinoma), A549 (lung carcinoma), BGC823 (gastric carcinoma) and MDAMB- 231 (breast carcinoma). The SAR analysis revealed that the anti-proliferative activity of the xanthones is substantially influenced by the position and number of attached hydroxyl and prenyl groups, and the presence of hydroxyl group ortho to the carbonyl function of xanthone scaffold contributes significantly to their cytotoxicity. The new prenylated xanthone 20 with a relatively simple structure, namely 1,3,8-trihydroxy-2-prenylxanthone, was found to exhibit potent antitumor activities comparable to α-mangostin against all the five cancer cell lines. Further mechanistic studies suggested that compound 20 induces apoptosis and causes cell cycle arrest at S phase in HepG2 cells. These results have highlighted compound 20 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents.
Keywords: Antitumor, Anti-Proliferative, Apoptosis, Cell Cycle Arrest, SAR, α-Mangostin, Xanthone
Medicinal Chemistry
Title:Synthesis, SAR and Biological Evaluation of Natural and Non-natural Hydroxylated and Prenylated Xanthones as Antitumor Agents
Volume: 8 Issue: 6
Author(s): Xiaojin Zhang, Xiang Li, Suofu Ye, Yu Zhang, Lei Tao, Yuan Gao, Dandan Gong, Meiyang Xi, Huyan Meng, Mingqian Zhang, Wenlei Gao, Xiaoli Xu, Qinglong Guo and Qidong You
Affiliation:
Keywords: Antitumor, Anti-Proliferative, Apoptosis, Cell Cycle Arrest, SAR, α-Mangostin, Xanthone
Abstract: In order to explore the detailed structure-activity relationship (SAR) around xanthone scaffold bearing hydroxyl and prenyl moieties, twenty-nine natural and non-natural hydroxylated and prenylated xanthones have been synthesized and evaluated for their in vitro anti-proliferative activities against five human cancer cell lines, including HepG2 (hepatocelluar carcinoma), HCT-116 (colon carcinoma), A549 (lung carcinoma), BGC823 (gastric carcinoma) and MDAMB- 231 (breast carcinoma). The SAR analysis revealed that the anti-proliferative activity of the xanthones is substantially influenced by the position and number of attached hydroxyl and prenyl groups, and the presence of hydroxyl group ortho to the carbonyl function of xanthone scaffold contributes significantly to their cytotoxicity. The new prenylated xanthone 20 with a relatively simple structure, namely 1,3,8-trihydroxy-2-prenylxanthone, was found to exhibit potent antitumor activities comparable to α-mangostin against all the five cancer cell lines. Further mechanistic studies suggested that compound 20 induces apoptosis and causes cell cycle arrest at S phase in HepG2 cells. These results have highlighted compound 20 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents.
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Cite this article as:
Zhang Xiaojin, Li Xiang, Ye Suofu, Zhang Yu, Tao Lei, Gao Yuan, Gong Dandan, Xi Meiyang, Meng Huyan, Zhang Mingqian, Gao Wenlei, Xu Xiaoli, Guo Qinglong and You Qidong, Synthesis, SAR and Biological Evaluation of Natural and Non-natural Hydroxylated and Prenylated Xanthones as Antitumor Agents, Medicinal Chemistry 2012; 8 (6) . https://dx.doi.org/10.2174/1573406411208061012
DOI https://dx.doi.org/10.2174/1573406411208061012 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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