Synthesis and Bioevaluation of Novel Oxa-Caged Garcinia Xanthones as Anti-Tumour Agents
Guangqiang Miao A , Junhai Ma A , Kan Yang A , Zhipeng Huang A , Qinlan Gu B , Yanjie Wang C , Qinglong Guo D E , Qidong You A D and Jinxin Wang A FA Key Laboratory of Drug Design and Optimization of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, China.
B Higher Vocational and Technical College, China Pharmaceutical University, Nanjing 210009, China.
C College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
D State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
E Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, China.
F Corresponding author. Email: jinxinwang@163.com
Australian Journal of Chemistry 68(6) 872-880 https://doi.org/10.1071/CH14328
Submitted: 23 May 2014 Accepted: 20 August 2014 Published: 11 November 2014
Abstract
Gambogic acid (GA), a special category of Garcinia xanthones, has attracted great attention owing to its striking bioactivities and unique structure. To further explore its structure–activity relationship, we prepared seven novel oxa-caged Garcinia xanthones that were for the first time varied at the C-2 position of B ring and at the C-21/22 or C-23 position of the prenyl group in the caged scaffold. Some compounds exhibited strong anti-proliferation activities in different cancer cell lines. Particularly, compound 8 showed more potent cytotoxic activity and better selectivity towards the A549 cell line than GA. Oxa-caged xanthones 8 was identified as an A549 cell apoptosis inducer through observations of morphological changes and Annexin-V/PI double-staining assay. Additionally, the structure–activity relationships of these new analogues were discussed.
References
[1] H. Auterhoff, H. Frauendorf, W. Liesenklas, C. Schwandt, Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1962, 295, 833.| Crossref | GoogleScholarGoogle Scholar |
[2] W. D. Ollis, M. V. J. Ramsay, I. O. Sutherland, S. Mongkolsuk, Tetrahedron 1965, 21, 1453.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2MXksVKju7w%3D&md5=aec6d8bcc75f2e125125b11ed84d4a29CAS |
[3] T. J. R. Weakley, S. K. Cai, H. Z. Zhang, J. F. W. Keana, J. Chem. Crystallogr. 2001, 31, 501.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XltFSksr8%3D&md5=78855002e10b270560303149c4b39badCAS |
[4] L. Zhao, Q. L. Guo, Q. D. You, Z. Q. Wu, H. Y. Gu, Biol. Pharm. Bull. 2004, 27, 998.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlvFKrsrY%3D&md5=1e5823a8783f3b5040b3b5093c0bfd5eCAS | 15256729PubMed |
[5] Y. Yang, L. Yang, Q. D. You, F. F. Nie, H. Y. Gu, L. Zhao, X. T. Wang, Q. L. Guo, Cancer Lett. 2007, 256, 259.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVOisLvE&md5=4aed7cc34c5d4ba4b6e2ac195131b2f3CAS | 17693016PubMed |
[6] S. Kasibhatla, K. A. Jessen, S. Maliartchouk, J. Y. Wang, N. M. English, J. Drewe, L. Qiu, S. P. Archer, A. E. Ponce, N. Sirisoma, S. C. Jiang, H. Z. Zhang, K. R. Gehlsen, S. X. Cai, D. R. Green, B. Tseng, Proc. Natl. Acad. Sci. USA 2005, 102, 12095.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXps1yqsr4%3D&md5=f0fd6c2e173249eca79ca4dc5a07c1bfCAS | 16103367PubMed |
[7] M. K. Pandey, B. Sung, K. S. Ahn, A. B. Kunnumakkara, M. M. Chaturvedi, B. B. Aggarwal, Blood 2007, 110, 3517.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlarur3M&md5=d46aeabbec4684f5666dff99a54bd00eCAS | 17673602PubMed |
[8] J. Yu, Q. L. Guo, Q. D. You, L. Zhao, H. Y. Gu, Y. Yang, H. W. Zhang, Z. Tan, X. Wang, Carcinogenesis 2006, 28, 632.
| Crossref | GoogleScholarGoogle Scholar | 17012222PubMed |
[9] N. Lu, Y. Yang, Q. D. You, Y. Ling, Y. Gao, H. Y. Gu, L. Zhao, X. T. Wang, Q. L. Guo, Cancer Lett. 2007, 258, 80.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1anu73M&md5=6e0c233617be4d96c13732ee6beb5cb3CAS | 17920764PubMed |
[10] T. F. Yi, Z. F. Yi, S. G. Cho, J. Luo, M. K. Pandey, B. B. Aggarwal, M. Y. Liu, Cancer Res. 2008, 68, 1843.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjtFOhsbw%3D&md5=12a1f9da1d15b5344becc4597819ff73CAS |
[11] Y. X. Qin, L. H. Meng, C. X. Hu, W. H. Duan, Z. L. Zuo, L. P. Lin, X. W. Zhang, J. Ding, Mol. Cancer Ther. 2007, 6, 2429.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVCgur7M&md5=f4f3c705ee6fa944cce0c1394bafe6bfCAS |
[12] Q. Zhao, Y. Yang, J. Yu, Q. D. You, S. Zeng, H. Y. Gu, N. Lu, Q. Qi, W. Liu, X. T. Wang, Q. L. Guo, Cancer Lett. 2008, 262, 223.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjtlWgsL0%3D&md5=eebc45cb13549739d52c59a75682c40cCAS | 18226852PubMed |
[13] J. Davenport, J. R. Manjarrez, L. Peterson, B. Krumm, B. S. J. Blagg, R. L. J. Matts, J. Nat. Prod. 2011, 74, 1085.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXksFGgurk%3D&md5=2d6f62d4386ca4ff6e8f44e86759e1e2CAS | 21486005PubMed |
[14] U. D. Palempalli, U. Gandhi, P. Kalantari, H. Vunta, R. J. Arner, V. Narayan, A. Ravindran, K. S. Prabhu, Biochem. J. 2009, 419, 401.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjs1yntLg%3D&md5=defba750ba299ecfc45d07df704347f4CAS | 19140805PubMed |
[15] H. Z. Zhang, S. Kasibhatla, Y. Wang, J. Herich, J. Guastella, B. Tseng, J. Drewe, S. X. Cai, Bioorg. Med. Chem. 2004, 12, 309.
| Crossref | GoogleScholarGoogle Scholar | 14723951PubMed |
[16] L. J. Lin, L. Z. Lin, J. M. Pezzuto, G. A. Cordell, Magn. Reson. Chem. 1993, 31, 340.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXlt1Cqt7c%3D&md5=945c30e731ccb5a3033e6e9f421936efCAS |
[17] O. Chantarasriwong, W. C. Cho, A. Batova, W. Chavasiri, C. Moore, A. L. Rheingold, E. A. Theodorakis, Org. Biomol. Chem. 2009, 7, 4886.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVSgtbnI&md5=6c860c6381c40eac3c454a2422f0b390CAS | 19907779PubMed |
[18] X. J. Wang, N. Lu, Q. Yang, D. D. Gong, C. J. Lin, S. L. Zhang, M. Y. Xi, Y. Gao, L. B. Wei, Q. L. Guo, Q. D. You, Eur. J. Med. Chem. 2011, 46, 1280.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsFWhu78%3D&md5=f389c989cb90084d050382020f94fd16CAS |
[19] Z. L. Liu, X. J. Wang, N. G. Li, H. P. Sun, J. X. Wang, Q. D. You, Tetrahedron 2011, 67, 4774.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXntFKnu7w%3D&md5=6b42b874117e98d0068859db5dbc4de0CAS |
[20] K. C. Nicolaou, J. Li, Angew. Chem., Int. Ed. 2001, 40, 4264.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXovFeisbo%3D&md5=003069feeb75d22e28d1d15705a5fe58CAS |
[21] E. J. Tisdale, I. Slobodov, E. A. Theodorakis, Org. Biomol. Chem. 2003, 1, 4418.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpsFymt7Y%3D&md5=c3e860d4315e5a52ed9358aceb776386CAS | 14727628PubMed |
[22] K. B. Wiberg, W. H. Richardson, J. Am. Chem. Soc. 1962, 84, 2800.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3sXotl2m&md5=d6d3e36d6573e19d62ae71baf93d1147CAS |
[23] V. D. Parker, Acta Chem. Scand., Ser. A 1981, 35b, 533.
| Crossref | GoogleScholarGoogle Scholar |
[24] M. Tilset, V. D. Parker, Acta Chem. Scand., Ser. A 1982, 36b, 123.
| Crossref | GoogleScholarGoogle Scholar |
[25] D. C. Magri, M. S. Workentin, Org. Biomol. Chem. 2003, 1, 3418.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnsFGku74%3D&md5=f073713ce105dc4a993b35f160a6a21aCAS | 14584806PubMed |
[26] H. P. Sun, F. H. Chen, X. J. Wang, Z. L. Liu, Q. Yang, X. J. Zhang, J. Zhu, L. Qiang, Q. L. Guo, Q. D. You, Eur. J. Med. Chem. 2012, 51, 110.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmtlSls70%3D&md5=eeacb15817858b13ec66949a34f6435cCAS |
[27] Q. L. Guo, Q. D. You, F. Feng, W. Y. Liu, Chinese Patent ZL01008049 2003.
[28] F. M. Freimoser, C. A. Jakob, M. Aebi, U. Tuor, Appl. Environ. Microbiol. 1999, 65, 3727.
| 1:CAS:528:DyaK1MXltVOltLk%3D&md5=d3f9cd4721bb168c3ec21b257d64cb8aCAS | 10427074PubMed |
