European Journal of Medicinal Chemistry
European Journal of Medicinal Chemistry
4 years ago

Design, synthesis and bioevaluation of antitubulin agents carrying diaryl-5,5-fused-heterocycle scaffold

Design, synthesis and bioevaluation of antitubulin agents carrying diaryl-5,5-fused-heterocycle scaffold
A series of 3,6-diaryl-1H-pyrazolo[5,1-c][1,2,4]triazoles (I) and 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (II) as antitubulin agents were designed, synthesized and bioevaluated. Compounds (II) 4a, 4d, 4f, 4j, 4l and 4n showed potent antiproliferative activity at sub-micromolar or nanomolar concentrations against SGC-7901, A549 and HT-1080 cell lines, indicating that the bioisosteric replacement of the carbonyl group and B-ring of SMART and ABI with a 5,5-fused-heterocycle scaffold successfully maintained potent antiproliferative activity. Compound 4f exhibited the most excellent antiproliferative activity against the three cancer cell lines (IC50 = 0.022–0.029 μM). Consistent with its potent antiproliferative activity, 4f also displayed excellent antitubulin activity (IC50 = 0.77 μM). Furthermore, compound 4f could dramatically affect cell morphology and microtubule networking, while cell cycle studies demonstrated that 4f significantly induced SGC-7901 cells arrest in G2/M phase. In addition, molecular docking studies supported the biological assay data and suggested that 4f may be a potential antitubulin agent.

Publisher URL: www.sciencedirect.com/science

DOI: S0223523417304361

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.