2. Academic Validation
  3. Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency

Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency

  • Bioorg Med Chem Lett. 2015 Jun 15;25(12):2584-8. doi: 10.1016/j.bmcl.2015.04.031.
Yue Wu 1,  Mingyang Hu 1,  Li Yang 1,  Xiang Li 1,  Jinlei Bian 1,  Fen Jiang 1,  Haopeng Sun 1,  Qidong You 2,  Xiaojin Zhang 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqd@163.com.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zxj@cpu.edu.cn.
PMID: 25958244 DOI: 10.1016/j.bmcl.2015.04.031
Abstract

DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation.

Keywords

Antitumor; Caged xanthones; Druglike; Gambogic acid; Natural-product-like.

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