Nature Communications
Nature Communications
5 years ago

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions
Tony Fröhlich, Mirjam Steingruber, Felix E. Held, Alexander Nesterov-Mueller, Svetlana B. Tsogoeva, Tobias C. Foertsch, Manfred Marschall, Corina Hutterer, Hanife Bahsi, Anton A. Guryev, Axel Kahnt, Daniela S. Mattes, Frank Hampel, Clemens von Bojničić-Kninski
Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC50 down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid–quinazoline hybrids and their application against HCMV (EC50 down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers.

Publisher URL: http://www.nature.com/articles/ncomms15071

DOI: 10.1038/ncomms15071

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.