2. Academic Validation
  3. Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities

Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities

  • Eur J Med Chem. 2013 Aug:66:171-9. doi: 10.1016/j.ejmech.2013.05.035.
Bin Yu 1,  Xiao-Jing Shi,  Jing-li Ren,  Xiao-Nan Sun,  Ping-Ping Qi,  Yuan Fang,  Xian-Wei Ye,  Meng-Meng Wang,  Jun-Wei Wang,  En Zhang,  De-Quan Yu,  Hong-Min Liu
Affiliations

Affiliation

  • 1 School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
PMID: 23792764 DOI: 10.1016/j.ejmech.2013.05.035
Abstract

Two series of steroidal dienamides 4a-q and 5a-f were designed, synthesized and evaluated for cytotoxic activities against five human Cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbon-carbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4a-q and 5a-f showed moderate to excellent cytotoxic activities with the IC₅₀ values ranging from 0.1 to 40 μM and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC₅₀ values less than 1 μM. Flow cytometry analysis demonstrated that compound 4c caused the cellular early Apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner.

Keywords

Apoptosis; Cell cycle arrest; Cytotoxicity; Dehydroepiandrosterone; Dienamides.

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