Rhopaladins' analogue (E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidines inhibit proliferation, promote apoptosis and down-regulation of E6/E7 mRNA in cervical cancer

Bioorg Med Chem Lett. 2020 Dec 1;30(23):127554. doi: 10.1016/j.bmcl.2020.127554. Epub 2020 Sep 17.

Abstract

The occurrence and development of cervical cancer threaten women's life and health, HPV-induced cervical cancer is a major health issue among women. We synthesized three Rhopaladins' analogue (E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidines via a tandem Ugi 4CC/SN cyclization with pyrrolidone as a core structure. In addition, the cytotoxicity of these new compounds in the cervical cancer cell line CaSki was studied by MTT assay. And then we chose one to research the apoptosis and the expression of E6/E7 mRNA in CaSki cells. The results indicated that the new compound can not only inhibited the proliferation of CaSki in dose-dependent and time-dependent manners but also induced the apoptosis, which may be related to the down-regulation of E6/E7 mRNA expression.

Keywords: Apoptosis; Cervical cancer; E6/E7; Proliferation; Rhopaladins' analogue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclization
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Papillomavirus E7 Proteins / genetics
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / pharmacology*
  • RNA, Messenger / metabolism*
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Papillomavirus E7 Proteins
  • Pyrrolidinones
  • RNA, Messenger