2. Academic Validation
  3. Identification of new potent anticancer derivatives through simplifying the core structure and modification on their 14- hydroxyl group from oridonin

Identification of new potent anticancer derivatives through simplifying the core structure and modification on their 14- hydroxyl group from oridonin

  • Eur J Med Chem. 2022 Mar 5;231:114155. doi: 10.1016/j.ejmech.2022.114155.
Junkai Liu 1,  Shaowen Xie 1,  Xiao Shao 1,  Songtao Xue 1,  Pian Du 1,  Hongyu Wu 1,  Shengtao Xu 1,  Zhe-Sheng Chen 2,  Dong-Hua Yang 2,  Jinyi Xu 3,  Hong Yao 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China.
  • 2 College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439, United States.
  • 3 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China. Electronic address: jinyixu@china.com.
  • 4 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China. Electronic address: hyao1989@sina.cn.
PMID: 35121201 DOI: 10.1016/j.ejmech.2022.114155
Abstract

The natural product oridonin has the potential to be a broad-spectrum antineoplastic agent. To develop oridonin analogues with high potency, a series of novel oridonin analogues were designed and synthesized by removing the multiple hydroxyl groups of parent compound. The representative analogues 14, 19, and 26 exhibited potent Anticancer effects against K562, MDA-MB-231, SMMC-7721, and MCF-7 cells. Further structural modification on their 14-OH generated more potent derivatives 16n, 21d, and 28d respectively, in which the IC50 value of compound 16n was 50-fold more potent than parent oridonin in K562 cells. Furthermore, compound 16n significantly induced the cell cycle arrest of K562 cells at the G2 phase and increased the fraction of apoptotic cells. Importantly, compounds 16n, 21d, and 28d exhibited good antitumor activities in H22 allograft mice in vivo. These results suggest that compounds 16n, 21d, and 28d deserve further development as promising candidates for the treatment of cancers.

Keywords

Anticancer; Natural products; Oridonin; SAR; Structural simplification.

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