ChemMedChem
ChemMedChem
5 years ago

Synthesis and Evaluation of In Vitro Biological Properties of Ferrocenyl Side-Chain-Decorated Paclitaxel

Chatchakorn Eurtivong, Homayon J. Arabshahi, Christian G. Hartinger, Damian Plażuk, Anna Makal, Sylwia Pawlędzio, Karolina Kowalczyk, Błażej Rychlik, Wojciech M. Ciszewski, Anna Wieczorek, Jóhannes Reynisson, Andrzej Błauż
Taxanes, including paclitaxel, are widely used in cancer therapy. In an attempt to overcome some of the disadvantages entailed with taxane chemotherapy, we devised the synthesis of ferrocenyl-decorated paclitaxels and studied their biological properties. The cytotoxic activity was measured in a panel of human cancer cell lines of different tissue origin including also multidrug resistant ones. A structure-activity study of paclitaxel ferrocenylation revealed that the N-benzoyl ferrocenyl substituted derivative was the most cytotoxic. In contrast, substitution of the 3'-phenyl group of paclitaxel with a ferrocenyl moiety led to formation of relatively less potent antiproliferative agents. However, they were able to overcome multidrug resistance as they were virtually unrecognized by ABCB1, a major cellular exporter of taxanes. Interestingly, redox properties of ferrocenyl derivatives seemed to play a less important role in the mode of action of the investigated compounds as there was no correlation between intracellular redox activity and cytotoxicity/cell cycle distribution of cells. The antiproliferative activity of ferrocenyl taxanes strongly depended on the substitution position and good polymerisation inducers, as confirmed by molecular docking, were usually more cytotoxic, while compounds with stronger pro-oxidative properties exhibited lower antiproliferative activity.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/cmdc.201700576

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.