Diversity-oriented synthesis and bioactivity evaluation of N-substituted ferrocifen compounds as novel antiproliferative agents against TNBC cancer cells Academic Article uri icon

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abstract

  • Ferrociphenols are characterized by the presence of a biologically active redox motif [ferrocenyl-ene-p-phenol], and are known to exhibit anticancer properties. Recent studies have identified a new series of ferrociphenols that bear an imido-type heterocycle at the terminus of a short alkyl chain, and which showed very strong antiproliferativity against multiple types of cancer cells. This work describes the syntheses and an SAR study of ferrociphenols bearing a diversity-based range of nitrogen-containing substituents on the alkyl chain. Preliminary oxidative metabolism experiments and ROS-related bioactivity measurements were also carried out to probe the origin of the cytotoxicity of the imido-ferrociphenols. Furthermore, an interesting dimerization phenomenon was observed in the X-ray crystal structure of the 2,3-naphthalenedicarboximidopropyl-ferrocidiphenol, 21, which may be a factor in decreasing its rate of oxidation to form the corresponding quinone methide, 21-QM, thereby affecting its antitumor activity. These results suggest that both the formation rate and the stability of QMs could affect the antiproliferative activity of their ferrociphenol precursors.

authors

  • Wang, Yong
  • Pigeon, Pascal
  • Li, Wei
  • Yan, Jiangkun
  • Dansette, Patrick M
  • Othman, Mohamed
  • Mcglinchey, Michael James
  • Jaouen, Gérard

publication date

  • April 2022