2. Academic Validation
  3. Synthesis of novel diterpenoid analogs with in-vivo antitumor activity

Synthesis of novel diterpenoid analogs with in-vivo antitumor activity

  • Eur J Med Chem. 2016 Sep 14;120:13-25. doi: 10.1016/j.ejmech.2016.04.071.
Ying-Ying Wang 1,  Yuan He 2,  Lian-Fang Yang 1,  Shi-Hong Peng 2,  Xiao-Long He 1,  Jin-Hua Wang 2,  Fang Lv 2,  Yun Hao 2,  Ming-Yao Liu 2,  Zhengfang Yi 3,  Wen-Wei Qiu 4
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
  • 2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • 3 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. Electronic address: [email protected].
  • 4 Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai, 200062, China. Electronic address: [email protected].
PMID: 27187855 DOI: 10.1016/j.ejmech.2016.04.071
Abstract

A lead compound 7 has antitumor effect, which was discovered by screening our small synthetic natural product-like compound (NPL) library. Based on the lead compound, a series of novel tricyclic diterpene analogs were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. To our delight, most aromatic amide compounds exhibited more potent antitumor activity than the lead compound. The most active compound 19 (QW30) showed an average IC50 0.33 μM, which was 15-fold more potent than the lead compound. Most of the compounds with potent antitumor activity displayed less toxic on normal human fibroblasts (HAF) in comparison with the tumor cell lines. Especially 19, its selectivity indexes (SI) between HAF and Cancer cell lines was 17.3 times better than the positive control compound podophyllotoxin. The Apoptosis, colony formation and transwell migration assays of 7 and 19 were performed on T47D cell line. The in-vivo antitumor effect of 19 was also observed in T47D tumor-bearing mice without obvious toxicity.

Keywords

Antitumor; Apoptosis; Colony formation; Diterpenoids; Migration; Tricyclic diterpene.

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  • HY-143659